Biology subjects

Hammer, J.

Publications and source records attributed to Hammer, J..

23 records · Page 2Linked to original sources

bioRxiv2022

Myosin 10 supports mitotic spindle bipolarity by promoting PCM integrity and supernumerary centrosome clustering

Myosin 10 (Myo10) is a member of the MyTH4/FERM domain family of unconventional, actin-based motor proteins. Studies have implicated Myo10 in supporting cell adhesion via its integrin-binding FERM domain, and spindle positioning and spindle pole integrity via its microtubule-binding MyTH4 domain. Here we characterized Myo10s contribution to mitosis using Myo10 knockout HeLa cells and MEFs isolated from a Myo10 knockout mouse. Most notably, both of these knockout cells exhibit a pronounced increase in the frequency of multipolar spindles. Staining of unsynchronized metaphase cells showed that the primary driver of spindle multipolarity in knockout MEFs and knockout HeLa cells lacking supernumerary centrosomes is PCM fragmentation, which creates y-tubulin-positive, centriole-negative microtubule asters that serve as additional spindle poles. For HeLa cells possessing supernumerary centrosomes, Myo10 depletion further accentuates spindle multipolarity by impairing centrosome clustering. These results argue, therefore, that Myo10 supports spindle bipolarity by maintaining PCM integrity in both normal and cancer cells, and by promoting supernumerary centrosome clustering in cancer cells. Finally, we present evidence that the defect in spindle pole integrity in Myo10 knockout cells is likely due to a defect in pole stability rather than pole maturation, and that Myo10 promotes supernumerary centrosome clustering at least in part by promoting cell adhesion during mitosis.

cell biology↗

bioRxiv2021

Wheat photosystem II heat tolerance responds dynamically to short and long-term warming

Heat-induced inhibition of photosynthesis is a key factor in declining wheat performance and yield. Variation in wheat heat tolerance can be characterised using the critical temperature (Tcrit) above which incipient damage to the photosynthetic machinery occurs. We investigated intraspecies variation and plasticity of wheat Tcrit under elevated temperature in field and controlled environment experiments. We also assessed whether intraspecies variation in wheat Tcrit mirrors patterns of global interspecies variation in heat tolerance reported for mostly wild, woody plants. In the field, wheat Tcrit varied through the course of a day, peaking at noon and lowest at sunrise, and increased as plants developed from heading to anthesis and grain filling. Under controlled temperature conditions, heat stress (36{degrees}C) was associated with a rapid rise in wheat Tcrit (i.e. within two hours of heat stress) that peaked after 3-4 days. These peaks in Tcrit indicate a physiological limitation to photosystem II heat tolerance. Analysis of a global dataset (comprising 183 Triticum and wild wheat (Aegilops) species) generated from the current study and a systematic literature review showed that wheat leaf Tcrit varied by up to 20{degrees}C (about two-thirds of reported global plant interspecies variation). However, unlike global patterns of interspecies Tcrit variation which has been linked to latitude of genotype origin, intraspecific variation in wheat Tcrit was unrelated to that. Yet, the observed genotypic variation and plasticity of wheat Tcrit suggests that this trait could be a useful tool for high-throughput phenotyping of wheat photosynthetic heat tolerance.

plant biology↗

bioRxiv2021

Intracerebral mechanisms explaining the impact of incidental feedback on mood state and risky choice

Identifying factors whose fluctuations are associated with choice inconsistency is a major issue for rational decision theory. Here, we investigated the neuro-computational mechanisms through which mood fluctuations may bias human choice behavior. Intracerebral EEG data were collected in a large group of participants (n = 30), while they were performing interleaved quiz and choice tasks. Neural baseline activity preceding choice onset was confronted first to mood level, estimated by a computational model integrating the feedbacks received in the quiz task, and then to the weighting of option attributes, in a computational model predicting risk attitude in the choice task. Results showed that 1) elevated broadband gamma activity (BGA) in the ventromedial prefrontal cortex (vmPFC) and dorsal anterior insula (daIns) was respectively signaling periods of high and low mood, 2) increased vmPFC and daIns BGA respectively promoted and tempered risk taking by overweighting gain versus loss prospects. Thus, incidental feedbacks induce brain states that correspond to different moods and bias the comparison of safe and risky options. More generally, these findings might explain why people experiencing positive (or negative) outcome in some part of their life tend to expect success (or failure) in any other.

neuroscience↗

bioRxiv2021

Dual regulation of the actin cytoskeleton by CARMIL-GAP

CARMIL (Capping protein Arp2/3 Myosin I Linker) proteins are multi-domain scaffold proteins that regulate actin dynamics by regulating the activity of Capping Protein (CP). Here we characterize CARMIL-GAP, a Dictyostelium CARMIL isoform that contains a ~130 residue insert that, by homology, is a GTPase activating (GAP) domain for Rho-related GTPases. Consistently, this GAP domain binds Dictyostelium Rac1a and accelerates its rate of GTP hydrolysis. CARMIL-GAP concentrates with F-actin in phagocytic cups and at the leading edge of chemotaxing cells, and CARMIL-GAP null cells exhibit pronounced defects in phagocytosis and chemotactic streaming. Importantly, these defects are fully rescued by expressing GFP-tagged CARMIL-GAP in CARMIL-GAP null cells. Finally, rescue with versions of CARMIL-GAP that lack either GAP activity or the ability to regulate CP show that while both activities contribute significantly to CARMIL-GAP function, the GAP activity plays the bigger role. Together, our results add to the growing evidence that CARMIL proteins influence actin dynamics by regulating signaling molecules as well as CP, and that the continuous cycling of the Rho GTPases nucleotide state is often required to drive Rho-dependent biological processes. SUMMARY STATEMENTThe assembly of actin filaments supports a wide array of fundamental cellular functions, including cell migration and phagocytosis. Actin assembly is controlled by a host of regulatory proteins, with Capping Protein being one of the most important. Capping Protein is in turn regulated by the CARMIL family of proteins. Actin assembly is also controlled by signaling pathways that often converge on Rho-related GTPases like Rac1. These GTPases cycle between an active, GTP-bound state and an inactive, GDP-bound state. Guanine nucleotide exchange factors (GEFs) and guanine nucleotide activating proteins (GAPs) drive Rho-related GTPases to their GTP-bound and GDP-bound states, respectively. Here we characterized a version of CARMIL that contains within it a GAP domain for Rac1. We show that CARMIL-GAP supports the actin-based processes of cell migration and phagocytosis. We also show that while CARMIL-GAPs ability to regulate Capping Protein and the nucleotide state of Rac1 are both important for its cellular functions, its ability to regulate Rac1 via its GAP domain plays the bigger role. Finally, our data support the emerging concept that the continuous cycling of Rho GTPases between their GTP- bound and GDP-bound states is often required to drive Rho-dependent biological processes.

cell biology↗

bioRxiv2017

Global and Local Dynamics of High-Gamma Activity Underlying Error Processing in the Human Brain Revealed by Noninvasive and Intracranial EEG

Error detection in motor behavior is a fundamental cognitive function heavily relying on cortical information processing. Neural activity in the high-gamma frequency band (HGB) closely reflects such local cortical processing, but little is known about its role in error processing, particularly in the healthy human brain. Here we characterize the error-related response of the human brain based on data obtained with noninvasive EEG optimized for HGB mapping in 31 healthy subjects (15 females, 16 males), and additional intracranial EEG data from 9 epilepsy patients (4 females, 5 males). Our findings reveal a comprehensive picture of the global and local dynamics of error-related HGB activity in the human brain. On the global level as reflected in the noninvasive EEG, the error-related response started with an early component dominated by anterior brain regions, followed by a shift to parietal regions, and a subsequent phase characterized by sustained parietal HGB activity. This phase lasted for more than 1 s after the error onset. On the local level reflected in the intracranial EEG, a cascade of both transient and sustained error-related responses involved an even more extended network, spanning beyond frontal and parietal regions to the insula and the hippocampus. HGB mapping appeared especially well suited to investigate late, sustained components of the error response, possibly linked to downstream functional stages such as error-related learning and behavioral adaptation. Our findings establish the basic spatio-temporal properties of HGB activity as a neural correlate of error processing, complementing traditional error-related potential studies.\n\nSignificance StatementThere is great interest to understand how the human brain reacts to errors in goal-directed behavior. An important index of cortical and subcortical information processing is fast oscillatory brain activity, particularly in the high-gamma band (above 50 Hz). Here we show that it is possible to detect signatures of errors in event-related high-gamma responses with noninvasive techniques, characterize these responses comprehensively, and validate the EEG procedure for the detection of such signals. In addition, we demonstrate the added value of intracranial recordings pinpointing the fine-grained spatio-temporal patterns in error-related brain networks. We anticipate that the optimized noninvasive EEG techniques as described here will be helpful in many areas of cognitive neuroscience where fast oscillatory brain activity is of interest.

neuroscience↗