Biology subjects

Ray, S.

Publications and source records attributed to Ray, S..

At least 91 records · Page 5Linked to original sources

bioRxiv2023

Gamma responses to colored natural stimuli can be predicted from local low-level stimulus features

The role of gamma rhythm (30-80 Hz) in visual processing is debated; stimuli like gratings and hue patches generate strong gamma, but many natural images do not. Could image gamma responses be predicted by approximating images as gratings or hue patches? Surprisingly, this question remains unanswered, since the joint dependance of gamma on multiple features is poorly understood. We recorded local field potentials and electrocorticogram from two monkeys while presenting natural images and parametric stimuli varying along several feature dimensions. Gamma responses to different grating/hue features were separable, allowing for a multiplicative model based on individual features. By fitting a hue patch to the image around the receptive field, this simple model could predict gamma responses to chromatic images across scales with reasonably high accuracy. Our results provide a simple "baseline" model to predict gamma from local image properties, against which more complex models of natural vision can be tested.

neuroscience↗

bioRxiv2023

GATA-regulated transcriptional program dictate cell fate equilibrium to establish the maternal-fetal exchange interface and fetal development

The placenta establishes a maternal-fetal exchange interface to transport nutrients and gases between the mother and the fetus. Establishment of this exchange interface relies on the development of multinucleated syncytiotrophoblasts (SynT) from trophoblast progenitors and defect in SynT development often leads to pregnancy failure and impaired embryonic development. Here, we show that mouse embryos with conditional deletion of GATA2 and GATA3 in labyrinth trophoblast progenitors have underdeveloped placenta and die [~] embryonic day 9.5 (E9.5). Single cell RNA Seq (scRNA-Seq) analysis revealed excessive accumulation of multipotent labyrinth trophoblast progenitors upon conditional deletion of GATA factors. The GATA factor-deleted multipotent progenitors were unable to differentiate to matured SynTs. We also show that the GATA factor-mediated priming of trophoblast progenitors for SynT differentiation is a conserved event during human placentation. Loss of either GATA2 or GATA3 in cytotrophoblast (CTB)-derived human trophoblast stem cells (human TSCs) drastically inhibits SynT differentiation potential. Identification of GATA2 and GATA3 target genes along with comparative bioinformatics analyses revealed that GATA factors directly regulate hundreds of common genes in human TSCs, including genes that are essential for SynT development and implicated in preeclampsia and fetal growth retardation. Thus, our study uncovers a conserved molecular mechanism, in which coordinated function of GATA2 and GATA3 promote trophoblast progenitor-to-SynT commitment ensuring establishment of the maternal-fetal exchange interface.

developmental biology↗

bioRxiv2023

Alpha and SSVEP power outperforms Gamma power in capturing Attentional Modulation in Human EEG

The effect of visual attention has been extensively studied using various techniques such as macaque neurophysiology that yields spikes and local field potential (LFP), and human electro/magneto encephalogram (EEG/MEG). Attention typically suppresses power at low frequencies such as alpha band (8-12 Hz) and increases power in gamma band (>30 Hz) in brain signals. In addition, EEG studies often use flickering stimuli that produce a specific measure called steady-state visually evoked potential (SSVEP), whose power also increases with attention. However, effectiveness of these various neural measures in capturing attentional modulation is unknown since the stimuli and task paradigms vary widely across these studies. In a recent macaque neurophysiology study with flickering stimuli, we found that the effect of attention was more salient in the gamma band and beyond of the LFP, compared to alpha or SSVEP. To compare this with human EEG, we designed an orientation change detection task where we presented both static and counterphasing stimuli of matched difficulty levels to male (N=15) and female (N=11) subjects, allowing us to compare attentional modulation of various measures under similar conditions. We report two main results. First, attentional modulation was comparable for SSVEP and alpha. Second, non-foveal stimuli produced weak gamma despite various stimulus optimizations and showed a negligible effect of attention although full-screen gratings showed robust gamma activity. Our results are useful for brain-machine-interfacing studies where suitable features depending on recording modality are used for decoding attention, and also provide clues about the spatial scales of neural mechanisms underlying attention. Significance StatementVarious neural measures such as alpha and gamma band power or SSVEP power capture signatures of visual attention. A systematic comparison of their effectiveness in capturing attentional modulation is important for understanding different neural computations underlying attention and for developing brain-machine-interfaces (BMIs) that can decode the focus of attention. Since stimulus configuration and task paradigms vary widely across visual attention studies, we recorded all the relevant neural signals during an attention task under similar stimulus and behavioral conditions in human EEG. In contrast to invasive recordings in which gamma outperforms other measures, our results show that in human EEG, attentional modulation of alpha and SSVEP are comparable, and non-foveal stimuli produce weak gamma which is not well modulated by attention.

neuroscience↗

bioRxiv2023

Innate attraction and aversion to odors in locusts

Many animals display innate preferences for some odors, but the physiological mechanisms underlying these preferences are poorly understood. Here, with behavioral tests, we establish a model system well suited to investigating olfactory mechanisms, the locust Schistocerca americana. We conducted open field two-choice tests with purely olfactory stimuli. In these tests, newly hatched locusts navigated toward, and spent time near, the source of a food odor blend, crushed wheat grass. In similar tests, we found that hatchlings avoided moderate concentrations of major individual components of the food blend odor, 1-hexanol and hexanal. They were neither attracted nor repelled by a lower concentration of 1-hexanol, but were moderately attracted to a low concentration of hexanal. These results establish that hatchlings have a strong, innate preference for food odor blend, but the valence of the blends individual components may be different and may change depending on the concentration. This suggests innate odor preferences may emerge from more complex processing pathways than labeled lines. Our results provide a useful entry point for an analysis of physiological mechanisms underlying innate sensory preferences.

animal behavior and cognition↗

bioRxiv2023

Neuron cilia constrain glial regulators to microdomains around distal neurons

Each glia interacts with multiple neurons, but the fundamental logic of whether it interacts with all equally remains unclear. We find that a single sense-organ glia modulates different contacting neurons distinctly. To do so, it partitions regulatory cues into molecular microdomains at specific neuron contact-sites, at its delimited apical membrane. For one glial cue, K/Cl transporter KCC-3, microdomain-localization occurs through a two-step, neuron-dependent process. First, KCC-3 shuttles to glial apical membranes. Second, some contacting neuron cilia repel it, rendering it microdomain-localized around one distal neuron-ending. KCC-3 localization tracks animal aging, and while apical localization is sufficient for contacting neuron function, microdomain-restriction is required for distal neuron properties. Finally, we find the glia regulates its microdomains largely independently. Together, this uncovers that glia modulate cross-modal sensor processing by compartmentalizing regulatory cues into microdomains. Glia across species contact multiple neurons and localize disease-relevant cues like KCC-3. Thus, analogous compartmentalization may broadly drive how glia regulate information processing across neural circuits.

neuroscience↗

bioRxiv2023

Slope of the power spectral density flattens at low frequencies (<150 Hz) with healthy aging but also steepens at higher frequency (>200 Hz) in human electroencephalogram

Brain signals such as electroencephalogram (EEG) often show oscillations at various frequencies, which are represented as distinct "bumps" in the power spectral density (PSD) of these signals. In addition, the PSD also shows a distinct reduction in power with increasing frequency, which pertains to aperiodic activity and is often termed as the "1/f" component. While a change in periodic activity in brain signals with healthy aging and mental disorders has been reported, recent studies have shown a reduction in the slope of the aperiodic activity with these factors as well. However, these studies only analysed PSD slopes over a limited frequency range (<100 Hz). To test whether the PSD slope is affected over a wider frequency range with aging and mental disorder, we collected EEG data with high sampling rate (2500 Hz) from a large population of elderly subjects (>49 years) who were healthy (N=217) or had mild cognitive impairment (MCI; N=11) or Alzheimers Disease (AD; N=5), and analysed the PSD slope till 800 Hz. Consistent with previous studies, the 1/f slope up to ~150 Hz reduced with healthy aging. Surprisingly, we found the opposite at higher frequencies (>200 Hz): the slope increased with age. This result was observed in all electrodes, for both eyes open and eyes closed conditions, and for different reference schemes. Slopes were not significantly different in MCI/AD subjects compared to age and gender matched healthy controls. Overall, our results constrain the biophysical mechanisms that are reflected in the PSD slopes in healthy and pathological aging. Significance StatementAperiodic activity in the brain is characterized by measuring the slope of the power spectrum of brain signals. This slope has been shown to flatten with healthy aging, suggesting an increase in some sort of "neural noise". However, this flattening has been observed only over a limited frequency range (<150 Hz). We found that at higher frequencies (>200 Hz), the opposite happens: the slope steepens with age. This occurs at all electrodes, irrespective of state and referencing techniques. However, the slope is unchanged in subjects with early Alzheimers Disease (AD) and their controls. Our results shed new light on the properties of neural noise and the neurophysiological processes affecting AD and the aperiodic activity.

neuroscience↗

bioRxiv2023

Healthy aging and cognitive impairment alter EEG functional connectivity in distinct frequency bands

Functional connectivity (FC) indicates the interdependencies between brain signals recorded from spatially distinct locations in different frequency bands, which is modulated by cognitive tasks and is known to change with aging and cognitive disorders. Recently, the power of narrow-band gamma oscillations induced by visual gratings has been shown to reduce with both healthy aging and in subjects with mild cognitive impairment (MCI). However, the impact of aging/MCI on stimulus-induced gamma FC has not been well studied. We recorded electroencephalogram (EEG) from a large cohort (N=229) of elderly subjects (>49 years) while they viewed large cartesian gratings to induce gamma oscillations and studied changes in alpha and gamma FC with healthy aging (N=218) and MCI (N=11). Surprisingly, we found that aging and disease changed power and FC in different ways. With healthy aging, alpha power did not change but FC decreased significantly. MCI reduced gamma but not alpha FC significantly compared with age and gender matched controls, even when power was matched between the two groups. Overall, our results show distinct effects of aging and disease on EEG power and FC, suggesting different mechanisms and the potential to use EEG stimulus-induced FC along with power for early diagnosis of Alzheimers Disease.

neuroscience↗

bioRxiv2023

Periplasmic stress contributes to a tradeoff between protein secretion and cell growth in E. Coli Nissile

Maximizing protein secretion is an important target in the design of engineered living systems. In this paper, we characterize a tradeoff between cell growth and per cell protein secretion in the curli biofilm secretion system of E Coli Nissile 1917. Initial characterization using 24-hour continuous growth and protein production monitoring confirms decreased growth rates at high induction leading to a local maximum in total protein production at intermediate induction. Propidium iodide staining at the endpoint indicates that cellular death is a dominant cause of growth reduction. Assaying variants with combinatorial constructs of inner and outer membrane secretion tags, we find that diminished growth at high production is specific to secretory variants associated with accumulation of protein containing the outer membrane transport tag in the periplasmic space. RNA sequencing experiments indicate upregulation of known periplasmic stress response genes in the highly secreting variant, further implicating periplasmic stress in the growth-secretion tradeoff. Overall, these results motivate additional strategies for optimizing total protein production and longevity of secretory engineered living systems.

synthetic biology↗

bioRxiv2022

Temporal characteristics of gamma rhythm constrain properties of noise in an inhibition-stabilized network model

Gamma rhythm refers to oscillatory neural activity between 30-80 Hz, often induced in visual cortex by presentation of stimuli such as iso-luminant hues or gratings. Further, the power and peak frequency of gamma depend on the properties of the stimulus such as size and contrast. Gamma also has a typical arch shape, with a narrow trough and a broad peak, which can be replicated by a self-oscillating Wilson-Cowan (WC) model operating in an appropriate regime. However, oscillations in this model are infinitely long, unlike physiological gamma that occurs in short bursts. Further, unlike the model, gamma is faster after stimulus onset and slows down over time. Here, we first characterized gamma burst duration in LFP data recorded from two monkeys while they viewed full screen iso-luminant hues. We then added different types of noise in the inputs to the WC model and tested how that affected duration and temporal dynamics of gamma. While the model failed with the often-used Poisson noise, Ornstein-Uhlenbeck (OU) noise applied to both the excitatory and inhibitory populations in the WC model replicated the duration and slowing of gamma, and also replicated the shape and stimulus dependencies. Therefore, temporal dynamics of gamma oscillations put constraints on the type and properties of underlying neural noise.

neuroscience↗

bioRxiv2022

High-resolution structures map the metal import pathway in an Nramp transporter

Transporters of the Nramp (Natural resistance-associated macrophage protein) family import divalent transition metal ions into cells of most organisms. By supporting metal homeostasis, Nramps prevent disorders related to metal insufficiency or overload. Previous studies revealed that Nramps take on a LeuT fold and identified the metal-binding site. We present high- resolution structures of Deinococcus radiodurans Nramp in three stable conformations of the transport cycle revealing that global conformational changes are supported by distinct coordination geometries of its physiological substrate, Mn2+, across conformations and conserved networks of polar residues lining the inner and outer gates. A Cd2+-bound structure highlights differences in coordination geometry for Mn2+ and Cd2+. Measurements of metal binding using isothermal titration calorimetry indicate that the thermodynamic landscape for binding and transporting physiological metals like Mn2+ is different and more robust to perturbation than for transporting the toxic Cd2+ metal.

biochemistry↗

bioRxiv2022

Large-scale capture of hidden fluorescent labels for training generalizable markerless motion capture models

Recent advances in deep learning-based markerless pose estimation have dramatically improved the scale and ease with which body landmarks can be tracked in studies of animal behavior. However, pose estimation for animals in a laboratory setting still faces some specific challenges. Researchers typically need to manually generate new training data for each experimental setup and visual environment, limiting the generalizability of this approach. With each network being trained from scratch, different investigators track distinct anatomical landmarks and analyze the resulting kinematic data in idiosyncratic ways. Moreover, much of the movement data is discarded: only a few sparse landmarks are typically labeled, due to the inherent scale and accuracy limits of manual annotation. To address these issues, we developed an approach, which we term GlowTrack, for generating large training datasets that overcome the relatively modest limits of manual labeling, enabling deep learning models that generalize across experimental contexts. The key innovations are: a) an automated, high-throughput approach for generating hidden labels free of human error using fluorescent markers; b) a multi-camera, multi-light setup for generating large amounts of training data under diverse visual conditions; and c) a technique for massively parallel tracking of hundreds of landmarks simultaneously using computer vision feature matching algorithms, providing dense coverage for kinematic analysis at a resolution not currently available. These advances yield versatile deep learning models that are trained at scale, laying the foundation for standardized behavioral pipelines and more complete scrutiny of animal movements.

neuroscience↗

bioRxiv2022

Phenol Sensing in Nature Modulated via a Conformational Switch Governed by Dynamic Allostery

NtrC family of proteins sense external stimuli and accordingly stimulate stress and virulence pathways via activation of associated {sigma}54-dependent RNA polymerases. Here, we establish that MopR, an NtrC protein, harbors a dynamic bi-directional electrostatic network that connects the phenol pocket to two distal regions, namely the "G-hinge" and the "allo-steric-linker". While G-hinge influences the entry of phenol, the allosteric-linker passes the signal to the downstream ATPase domain. Phenol binding induces a rewiring of the electrostatic connections by eliciting dynamic allostery, and it was demonstrated that perturbation of the core relay residues results in a complete loss of ATPase stimulation. A mutation of the G-hinge,[~]20[A] from the phenol pocket, demonstrated altered flexibility by shifting the pattern of conformational states accessed, leading to a protein with 7-fold enhanced phenol binding ability and enhanced transcriptional activation. A global analysis illustrates that dynamic allostery-driven conserved community networks are universal and evolutionarily conserved across species.

biochemistry↗

bioRxiv2022

Mass photometric detection and quantification of nanoscale α-synuclein phase separation

-Synuclein (-Syn) liquid-liquid phase separation (LLPS) leads to irreversible amyloid fibril formation associated with Parkinsons disease pathogenesis. Critical concentrations of -Syn LLPS are relatively high under physiological solution conditions. Moreover, -Syn exhibits delayed LLPS kinetics under certain conditions which deviates from the behaviour predicted by classical homogeneous nucleation theory. In the current body of work, using interferometric light scattering (iSCAT), also known as mass photometry, we experimentally probe that -Syn can form nanoscale phase separated assemblies/clusters, containing tens to hundreds of molecules-- both above and below the critical LLPS concentration down to physiologically relevant scales. The formation of these clusters is instantaneous, even under conditions where the formation of microscopically visible droplets takes several days. However, they account for a very small volume fraction below saturation concentration. The slow growth of the nanoclusters can be attributed to a kinetic barrier which can be overcome by increasing the solution temperature to just below the droplet melting point. We provide reasons for caution in quantifying dilute phase concentrations for -Syn LLPS samples containing nanoscale droplets--which can only be separated using ultracentrifugation. In addition, we also delineate that the presence of certain surfaces facilitates -Syn droplet nucleation under conditions of delayed kinetics but is not a mandatory prerequisite for nanocluster formation. Taken together, our findings reveal that phase separation of -Syn occurs at a wider range of solution conditions than predicted so far and provides an important step towards understanding -Syn LLPS within physiological scales. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=197 SRC="FIGDIR/small/490467v1_ufig1.gif" ALT="Figure 1"> View larger version (75K): org.highwire.dtl.DTLVardef@b355org.highwire.dtl.DTLVardef@1fdc4bdorg.highwire.dtl.DTLVardef@17f8aa8org.highwire.dtl.DTLVardef@682598_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2022

Combinatorial interactions of Hox genes establish appendage diversity of the amphipod crustacean Parhyale hawaiensis

Hox genes establish regional identity along the anterior-posterior axis in diverse animals. Changes in Hox expression can induce striking homeotic transformations, where one region of the body is transformed into another. Previous work in Drosophila has demonstrated that Hox cross-regulatory interactions are crucial for maintaining proper Hox expression. One major mechanism is the phenomenon of "posterior prevalence", wherein anterior Hox genes are repressed by more posterior Hox genes. Loss of posterior Hox expression under this model would predict posterior-to-anterior transformations, as is frequently observed in Drosophila. While posterior prevalence is thought to occur in many animals, studies of such Hox cross-regulation have focused on a limited number of organisms. In this paper, we examine the cross-regulatory interactions of three Hox genes, Ultrabithorax (Ubx), abdominal-A (abd-A), and Abdominal-B (Abd-B) in patterning thoracic and abdominal appendages in the amphipod crustacean Parhyale hawaiensis. Studies of Hox function in Parhyale have previously revealed two striking phenotypes which differed markedly from what a "posterior prevalence" model would predict, including non-contiguous and anterior-to-posterior transformations. We probe the logic of Parhyale Hox cross-regulation by using CRISPR/Cas9 to systematically examine all combinations of Ubx, abd-A, and Abd-B loss of function in Parhyale. By analyzing homeotic phenotypes and examining the expression of additional Hox genes, we reveal Hox cross-regulatory interactions in Parhyale. From these data, we also demonstrate that some Parhyale Hox genes function combinatorially to specify posterior limb identity, rather than abiding by a posterior prevalence mechanism. These results provide evidence that combinatorial Hox interactions may be responsible for the tremendous body plan diversity of crustaceans. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=192 SRC="FIGDIR/small/485717v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@16bfc85org.highwire.dtl.DTLVardef@8f859eorg.highwire.dtl.DTLVardef@8d7892org.highwire.dtl.DTLVardef@1e6c9f0_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2022

Hippo Signaling Cofactor, WWTR1, at the Crossroads of Human Trophoblast Progenitor Self-Renewal and Differentiation.

Healthy progression of human pregnancy relies on cytotrophoblast progenitor (CTB) self-renewal and their differentiation towards multi-nucleated syncytiotrophoblasts (STBs) and invasive extravillous trophoblasts (EVTs). However, underlying molecular mechanisms that fine-tune CTB self-renewal or direct their differentiation towards STBs or EVTs during human placentation are poorly defined. Here, we show that hippo signaling cofactor WW Domain Containing Transcription Regulator 1 (WWTR1) is a master regulator of trophoblast fate choice during human placentation. Using human trophoblast stem cells (human TSCs), primary CTBs and human placental explants, we demonstrate that WWTR1 promotes self-renewal in human CTBs and is essential for their differentiation to EVTs. In contrast, WWTR1 prevents induction of STB fate in undifferentiated CTBs. Our single-cell RNA-sequencing analyses in first-trimester human placenta along with mechanistic analyses in human TSCs revealed that WWTR1 fine-tunes trophoblast fate by directly regulating Wnt signaling components. Importantly, our analyses of placentae from pathological pregnancies show that extreme preterm birth (gestational time [≤]28weeks) and intrauterine growth restriction along with preeclampsia (IUGR/PE) are often associated with loss of WWTR1 expression in CTBs. In summary, our findings establish a critical importance of WWTR1 at the crossroads of human trophoblast progenitor self-renewal vs. differentiation. It plays positive instructive roles to promote CTB self-renewal and EVT differentiation and safeguards undifferentiated CTBs from obtaining the STB fate. SIGNIFICANCEHuman pregnancy relies on formation of the transient organ placenta and trophoblast cells are the major building blocks of the placenta. A defect in trophoblast progenitor self-renewal or their differentiation is associated with either pregnancy loss or pathological pregnancies, yet underlying molecular mechanisms that regulate trophoblast differentiation are poorly understood. In this study, we discovered that WWTR1, a transcription cofactor and a component of conserved Hippo signaling pathway, optimizes trophoblast progenitor self-renewal and is essential for their differentiation into the invasive extravillous trophoblast cell lineage. Our findings establish WWTR1 as a critical regulator for success in human placentation and progression of a healthy pregnancy.

developmental biology↗

bioRxiv2022

Local interactions between steady-state visually evoked potentials at nearby flickering frequencies

Steady-state visually evoked potentials (SSVEP) are widely used to index top-down cognitive processing in human electroencephalogram (EEG) studies. Typically, two stimuli flickering at different temporal frequencies (TFs) are presented, each producing a distinct response in the EEG at its flicker frequency. However, how SSVEP responses in EEG are modulated in the presence of a competing flickering stimulus just due to sensory interactions is not well understood. We have previously shown in local field potentials (LFP) recorded from awake monkeys that when two overlapping full screen gratings are counter-phased at different TFs, there is an asymmetric SSVEP response suppression, with greater suppression from lower TFs, which further depends on the relative orientations of the gratings (stronger suppression and asymmetry for parallel compared to orthogonal gratings). Here, we first confirmed these effects in both male and female human EEG recordings. Then, we mapped the response suppression of one stimulus (target) by a competing stimulus (mask) over a much wider range than the previous study. Surprisingly, we found that the suppression was not stronger at low frequencies in general, but systematically varied depending on the target TF, indicating local interactions between the two competing stimuli. These results were confirmed in both human EEG and monkey LFP and electrocorticogram (ECoG) data. Our results show that sensory interactions between multiple SSVEPs are more complex than shown previously and are influenced by both local and global factors, underscoring the need to cautiously interpret the results of studies involving SSVEP paradigms.

neuroscience↗

bioRxiv2022

Liquid condensate is a common state of proteins and polypeptides at the regime of high intermolecular interactions

Liquid-liquid phase separation (LLPS) has emerged as a crucial biological mechanism for sequestering macromolecules (such as proteins and nucleic acids) into membraneless organelles in cells. Unstructured and intrinsically disordered domains are known to facilitate multivalent interactions driving protein LLPS. We hypothesized that LLPS could be an intrinsic property of proteins/polypeptides at their high intermolecular interaction regime. To examine this, we studied many (a total of 23) proteins/polypeptides with different structures and sequences for LLPS study using molecular crowder polyethylene glycol (PEG-8000). We showed that all proteins and even highly charged polypeptides (under study) can undergo liquid condensate formation, however with different phase space and conditions. Using a single component and combinations of protein multicomponent (co-LLPS) systems, we establish that a variety of intermolecular interactions can drive proteins/polypeptides LLPS.

biophysics↗

bioRxiv2022

Functional Requirements for a Samd14-Capping Protein Complex in Stress Erythropoiesis

Acute anemia induces rapid expansion of erythroid precursors and accelerated differentiation to replenish erythrocytes. Paracrine signals - involving cooperation between SCF/c-Kit signaling and other signaling inputs - are required for the increased erythroid precursor activity in anemia. Our prior work revealed that the Sterile Alpha Motif (SAM) Domain 14 (Samd14) gene increases the regenerative capacity of the erythroid system and promotes stress-dependent c-Kit signaling. However, the mechanism underlying Samd14s role in stress erythropoiesis is unknown. We identified a protein- protein interaction between Samd14 and the - and {beta} heterodimers of the F-actin capping protein (CP) complex. Knockdown of the CP {beta} subunit increased erythroid maturation in ex vivo cultures and decreased colony forming potential of stress erythroid precursors. In a genetic complementation assay for Samd14 activity, our results revealed that the Samd14-CP interaction is a determinant of erythroid precursor cell levels and function. Samd14-CP promotes SCF/c-kit signaling in CD71med spleen erythroid precursors. Given the roles of c-Kit signaling in hematopoiesis and Samd14 in c-Kit pathway activation, this mechanism may have pathological implications in acute/chronic anemia.

cell biology↗