Biology subjects

Jahn, O.

Publications and source records attributed to Jahn, O..

18 recordsLinked to original sources

bioRxiv2026

Invariant scaling of the Species Abundance Distribution in observed and simulated marine plankton communities

Marine plankton are functionally diverse and span over five orders of magnitude in diameter, with important consequences for marine biogeochemical cycles. Marine ecosystem simulations are beginning to resolve this diversity; however, major uncertainties persist regarding the structure and function of planktonic ecosystems. Here we diagnosed plankton Species Abundance Distributions (SADs) in large-scale surveys and in a global, mechanistic plankton community simulation. The fitted slopes of the SADs vary by less than 10% across latitude, season, and biome in both observations and the simulation. Fitting parametric SADs further reveals spatial structure in the shape and functional form of the SAD aligned with established biogeographic provinces. Together, these results demonstrate a largely invariant structure of marine plankton communities that persists despite strong environmental gradients and taxonomic turnover. These findings suggest that the emergent shape and scaling of plankton SADs reflect fundamental constraints on community assembly and provide a compact quantitative diagnostic for planktonic ecosystem structure.

ecology↗

bioRxiv2026

Implicit representation of viruses fails to capture impacts of virus-induced mortality in global marine ecosystem models

Virus-induced mortality influences plankton biogeography, community structure, and ocean elemental cycles. However, quantification of virus-induced impacts remains challenging and often limited in scope. An alternative to explicit inclusion of viral dynamics in biogeochemical models is to represent viral effects implicitly, by assuming that mortality increases quadratically with cell or biomass density. Using 1D and 3D configurations of a nutrient-phytoplankton-zooplankton-virus-detritus (NPZVD) model, we ask whether the implicit quadratic mortality assumption captures patterns of virus-induced mortality, and its impact on biomass and primary production. The 1D water-column configuration shows that, at the onset of the spring bloom, the quadratic, implicit representation imposes viral losses on phytoplankton density instantaneously, which limits spring bloom formation. This is in contrast to the explicit representation, which allows initial bloom formation to proceed unhampered initially, but imposes a far stronger viral mortality later in the year driven by high rates of host-virus contact due to high phytoplankton and viral densities that take time to accumulate. By comparison to the implicit model, explicit resolution of viruses within the 3D global model shows strong potential for viruses to prematurely terminate phytoplankton blooms. Biogeochemical models would therefore benefit from explicit representation of viral infection insofar as models can be developed that adequately recapitulate in situ observations. Key PointsO_LIGlobal model reveals significant spatial heterogeneity arising from explicit, rather than implicit, representation of viruses C_LIO_LIImplicit representation of viral dynamics fails to capture the potential for viruses to terminate phytoplankton blooms C_LIO_LIBiogeochemical models require explicit representation of viruses to adequately simulate their effect on marine systems C_LI

microbiology↗

bioRxiv2026

Fatty acid binding protein-8 (FABP8/PMP2) reveals molecular heterogeneity of myelin sheaths in the human CNS

Myelin is classically viewed as a uniform axon-insulating membrane, yet its molecular composition may differ between species and even within one species. Fatty acid binding protein-8 (FABP8/PMP2) was previously identified in CNS myelin of humans but not mice. Here we show that FABP8/PMP2 is a defining feature of CNS myelin in humans and old-world-monkeys, but absent from CNS myelin in other mammals, indicating evolutionary neofunctionalization of this lipid-binding protein in the primate lineage. In the human CNS, FABP8/PMP2 marks a subset of myelin sheaths that preferentially ensheath large-diameter axons, revealing sheath-to-sheath molecular heterogeneity correlated with axonal geometry. Chromatin is accessible at the PMP2/Pmp2 gene locus in oligodendrocytes of humans but not mice. Human oligodendrocytes intrinsically express FABP8/PMP2 when transplanted into mouse brains, demonstrating species-specific competence independent of environmental cues. Humanized transgenic mice expressing FABP8/PMP2 in oligodendrocytes form morphologically normal but developmentally transiently thicker myelin sheaths, and show elevated cholesterol content in purified myelin. Because FABP8/PMP2 binds cholesterol, we propose that its emergence in primate CNS myelin contributes to the cholesterol enrichment of human myelin. Thus, CNS myelin protein composition is evolvable and modular, with relevance for myelin lipids and morphology, and previously unrecognized complexity in neuron-glia co-adaptation. Main points- Fatty acid binding protein 8 (FABP8/PMP2) is present in CNS myelin of humans and old-world monkeys - PMP2 defines sheath-to-sheath heterogeneity in the human CNS - PMP2-immunopositive myelin ensheaths large-diameter axons - Human oligodendrocytes intrinsically express PMP2 upon transplantation into mice - Humanized PMP2-transgenic mice show thicker myelin and altered myelin lipid composition

neuroscience↗

bioRxiv2026

Viral impacts on plankton standing stocks, primary productivity, and biogeochemistry in a model ocean

Viral lysis fuels the microbial loop by enhancing organic matter recycling (via the viral shunt) and can redirect organic matter toward export (via the viral shuttle). However, the global impact of viral infection mediated by shunt and shuttle pathways remains unclear. Here, we implemented viral infection and lysis processes in a global ocean ecosystem model, including a single phytoplankton (representing Prochlorococcus), virus (representing cyanophage), and nanozooplankton. Despite low but plausible levels of viral infection, high shunt efficiencies generated enhanced-productivity regions covering up to approximately one-half of the global ocean. For lower viral shunt efficiencies, the enhanced-productivity regions contracted abruptly, accompanied by steady declines in productivity. Viral-mediated increases in primary productivity reduced the extent of tropical oligotrophic regions at high shunt efficiencies, while lower efficiencies expanded oligotrophic areas. These results provide a path forward to developing predictive models of how viral infection and the fate of cellular lysates shape global ocean ecosystems.

ecology↗

bioRxiv2025

Cellular-level control on global ocean deoxygenation driven by phytoplankton ecophysiology

Phytoplankton elemental composition shapes the distribution of dissolved nutrient concentrations and thus plays a key role in ocean biogeochemistry. While the carbon-to-nitrogen-to-phosphorus ratio (C:N:P) in marine phytoplankton has been extensively studied, the hydrogen (H) and oxygen (O) content have received less attention despite their critical role in determining dissolved oxygen (O2) consumption rates in the ocean. Here, we estimated the elemental composition of marine phytoplankton, including the H and O content, from first principles, using a cellular allocation model embedded in a global ocean model. We estimated that an average phytoplankton cell has a chemical formula of C107H190N16O53P, with an O2 demand of 149 mol O2/mol P and respiration quotients of 1.40 mol O2/mol C, suggesting a lower H and O content, and higher O2 demand than commonly assumed. We found global variations in the O2 demand of organic matter respiration driven by population structure and cellular reorganisation under different environmental conditions. By testing how shifts in the macromolecular composition of phytoplankton cells affect the oceans O2 budget, we found that O2 consumption increases significantly when shifting cell composition from carbohydrate-rich to protein- or lipid-rich cells. As a result, low-O2 (hypoxic) zones in the ocean expanded by 75%. These findings demonstrate that cellular-level processes in marine phytoplankton shape the global O2 cycle and large-scale patterns of ocean biogeochemistry.

ecology↗

bioRxiv2025

Adaptor protein complex 2 (AP2) participates in biogenesis and homeostasis of myelin sheaths in the central nervous system

Myelination of CNS axons requires oligodendrocytes to undergo extensive morphological changes by producing large amounts of myelin membrane with defined protein composition and structure. The formation of myelin sheaths thus involves efficient trafficking and sorting of future myelin constituents via vesicles that fuse with prospective myelin membranes by exocytotic mechanisms. However, the functional relevance of other trafficking steps in oligodendocytes for myelin biogenesis is largely unknown. Here, we followed the hypothesis that developmental myelination involves endocytic mechanisms. In this model, Golgi-derived vesicles fuse with the oligodendroglial plasma membrane, from which myelin constituents are retrieved by endocytosis into endosomal/lysosomal organelles before their final integration into the growing sheath. Considering that adaptor protein complex-2 subunit-{micro} (AP2M) facilitates AP2-dependent endocytosis, we recombined the Ap2m-gene in myelin-forming oligodendrocytes, causing both hypomyelination and specific changes in the myelin proteome. Most strikingly, lysosomal membrane proteins accumulate in the abaxonal (outermost) myelin layer, identifying this membrane as an active site for retrieving constituents from myelin sheaths. These data demonstrate that the AP2 complex serves a critical function in developmental myelination in vivo. Unexpectedly, we also observed pathological myelin outfoldings indicative of focal hypermyelination. Consistent with the hypothesis that this phenotype reflects impaired maintenance rather than biogenesis of myelin sheaths, recombination of the Ap2m-gene in oligodendrocytes of adult mice caused late-onset progressive focal hypermyelination. These results indicate that, in addition to astrocytic and microglial phagocytosis, oligodendrocytes cell-autonomously contribute to maintaining the structure of healthy myelin sheaths via AP2-dependent mechanisms.

neuroscience↗

bioRxiv2025

Epitope Sequence and Modification Fingerprints of Anti-Aβ Antibodies

A hallmark of Alzheimers disease (AD), the most common form of dementia, is the progressive accumulation of amyloid-beta (A{beta}) peptides across distinct brain regions. Anti-A{beta} antibodies (A{beta}-Abs) targeting specific A{beta} variants are essential tools for AD research, diagnostics, and therapy. The monoclonal antibodies Aducanumab, Lecanemab, and Donanemab have recently been approved as the first disease-modifying treatments for early AD, highlighting the clinical importance of their exact binding profiles. In this study, we systematically characterized the binding and modification requirements of 20 A{beta}-Abs, including biosimilars of Aducanumab, Lecanemab, and Donanemab, across monomeric, oligomeric, and aggregated A{beta} forms. Array-based analysis of 20,000 modified A{beta} peptides defined binding epitopes at single-residue resolution and revealed the impact of sequence variation, including familial AD mutations, as well as diverse post-translational modifications (PTMs). Notably, genetic variants such as H6R impaired binding of therapeutic A{beta}-Abs like Aducanumab. Donanemab showed strong preference for pyroglutamate-modified A{beta}pE3-10, while Lecanemab and Aducanumab exhibited aggregation- and sequence-context-dependent binding requirements. Comparison of peptide binding profiles with binding of full-length and aggregated A{beta} via immunoprecipitation-mass spectrometry, capillary immunoassays, Western blotting, and immunohistochemistry on AD brain tissue revealed distinct aggregation-dependent binding behaviours. The valency- and context-dependence of Aducanumab binding, together with its preference for Ser8-phosphorylated A{beta}, supports a dimerization-mediated binding mechanism. For Lecanemab, our data suggest that additional structural contributions beyond the minimal N-terminal epitope are required for binding to aggregated A{beta}, which remain to be fully resolved. Together, this work provides the most comprehensive dataset to date on aggregation-dependent sequence and modification selectivity of A{beta}-Abs. By integrating mutational, PTM, and aggregation contexts in a unified experimental framework, we establish a resource that enables rational selection of antibodies for research and diagnostic applications, and offers mechanistic insights that may inform the design and optimization of future therapeutic antibodies in AD.

biochemistry↗

bioRxiv2024

Worldwide soundscape ecology patterns across realms

Abstract and keywordsO_ST_ABSAimC_ST_ABSThe urgency for remote, reliable, and scalable biodiversity monitoring amidst mounting human pressures on ecosystems has sparked worldwide interest in Passive Acoustic Monitoring (PAM), which can track life underwater and on land. However, we lack a unified methodology to report this sampling effort and a comprehensive overview of PAM coverage to gauge its potential as a global research and monitoring tool. To remediate this, we created the Worldwide Soundscapes project, a collaborative network and growing database comprising metadata from 409 datasets across all realms (terrestrial, marine, freshwater, and subterranean). LocationWorldwide, 12 200 sites, all ecosystems. Time period1991 to present. Major taxa studiedAll soniferous taxa. MethodsWe synthesise sampling coverage across spatial, temporal, and ecological scales using metadata describing sampling locations, deployment schedules, focal taxa, and recording parameters. We explore global trends in biological, anthropogenic, and geophysical sounds based on 168 recordings from twelve ecosystems across all realms. ResultsTerrestrial sampling is spatially denser (45 sites/Mkm2) than aquatic sampling (0.3 and 1.8 sites/Mkm2 in oceans and fresh water) with only two subterranean datasets. Although diel and lunar cycles are well-covered in all realms, only marine datasets (56%) comprehensively sample all seasons. Across twelve ecosystems, biological sounds show contrasting diel patterns, decline with distance from the equator and negatively correlate with anthropogenic sounds. Main conclusionsPAM can inform macroecology studies as well as global conservation and phenology syntheses, but representation can be improved by expanding terrestrial taxonomic scope, sampling coverage in the high seas and subterranean ecosystems, and spatio-temporal replication in freshwater habitats. Overall, this global PAM network holds promise to support global biodiversity research and monitoring efforts.

ecology↗

bioRxiv2023

DAR1 - An Easy to Use, Single-Box, Configuration of a Global Scale Biogeochemical Ecosystem Model

Global scale biogeochemical ocean models, such as the MIT-Darwin model, are important tools to help us understand the mechanisms which drive elemental cycles and marine planktonic ecosystems. However, these models are difficult to use and their complex outputs can make them tricky to interpret. Here we present DAR1, an easy-to-use framework written in Julia that maintains all of the ecological and chemical complexity present in the MIT-Darwin model while removing the computational and physical complexity. We provide three studies to showcase DAR1 features: a framework for nutrient amendment bottle experiments; a test of steady state assumptions on plankton community structure at the global scale; and a test of theoretical predictions for the niche space of nitrogen-fixing plankton. DAR1 is ideal for model based testing of ecological predictions from field and experimental observations while also providing access to modeling tools for the non-expert.

ecology↗

bioRxiv2022

Phosphorylation Determines Whether Neuroligin-3 is at Excitatory or Inhibitory Synapses in Different Regions of the Brain

Neuroligin-3 is a postsynaptic adhesion molecule involved in development, function, and pathologies of synapses in the brain. It is a genetic cause of autism and a potent component of the tumor microenvironment in gliomas. There are four Neuroligins that operate at distinct synapse types, selectively interacting with presynaptic adhesion and postsynaptic scaffold proteins. We investigated the subcellular localization and scaffold specificities of synaptic Neuroligin-3 and demonstrate an unexpected pattern of localization to excitatory synapses in cortical areas, and inhibitory synapses in subcortical areas. Using phosphoproteomics, we identify Neuroligin-3-specific serine phosphorylation in cortex and hippocampus that obstructs a key binding site for inhibitory synapse scaffolds. Using in utero CRISPR/Cas9 knockout and replacement with phosphomimetic mutants, we demonstrate that phosphorylation at this site determines excitatory versus inhibitory synapse localization of Neuroligin-3 in vivo. Our data reveal a mechanism that differentially regulates the balance of Neuroligin-3 between excitatory and inhibitory synapses, adding to our emerging understanding of their role in the development of brain connectivity and associated pathologies.

neuroscience↗

bioRxiv2022

Myelin lipids as nervous system energy reserves

Neuronal functions and impulse propagation depend on the continuous supply of glucose1,2. Surprisingly, the mammalian brain has no obvious energy stores, except for astroglial glycogen granules3. Oligodendrocytes make myelin for rapid axonal impulse conduction4 and also support axons metabolically with lactate5-7. Here, we show that myelin itself, a lipid-rich membrane compartment, becomes a local energy reserve when glucose is lacking. In the mouse optic nerve, a model white matter tract, oligodendrocytes survive glucose deprivation far better than astrocytes, by utilizing myelin lipids which requires oxygen and fatty acid beta-oxidation. Importantly, fatty acid oxidation also contributes to axonal ATP and basic conductivity. This metabolic support by fatty acids is an oligodendrocyte function, involving mitochondria and myelin-associated peroxisomes, as shown with mice lacking Mfp2. To study reduced glucose availability in vivo without physically starving mice, we deleted the Slc2a1 gene from mature oligodendrocytes. This caused a significant decline of the glucose transporter GLUT1 from the myelin compartment leading to myelin sheath thinning. We suggest a model in which myelin turnover under low glucose conditions can transiently buffer axonal energy metabolism. This model may explain the gradual loss of myelin in a range of neurodegenerative diseases8 with underlying hypometabolism9.

neuroscience↗

bioRxiv2022

Conservation and divergence of myelin proteome and oligodendrocyte transcriptome profiles between humans and mice

Human myelin disorders are commonly studied in mouse models. Since both clades evolutionarily diverged approximately 85 million years ago, it is critical to know to what extent the myelin protein composition has remained similar. Here we use quantitative proteomics to analyze myelin purified from human white matter and find that the relative abundance of the structural myelin proteins PLP, MBP, CNP and SEPTIN8 correlates well with that in C57Bl/6N- mice. Conversely, multiple other proteins were identified exclusively or predominantly in human or mouse myelin. This is exemplified by peripheral myelin protein-2 (PMP2), which was specific to human CNS myelin, while tetraspanin-2 (TSPAN2) and connexin-29 (CX29/GJC3) were confined to mouse myelin. Assessing published scRNA-seq-datasets, human and mouse oligodendrocytes display well-correlating transcriptome profiles but divergent expression of distinct genes including Pmp2, Tspan2 and Gjc3. Species-dependent diversity of oligodendroglial mRNA-expression and myelin protein composition can be informative when translating from mouse models to humans.

neuroscience↗

bioRxiv2021

Progressive axonopathy when oligodendrocytes lack the myelin protein CMTM5

Oligodendrocytes facilitate rapid impulse propagation along the axons they myelinate and support their long-term integrity. However, the functional relevance of many myelin proteins has remained unknown. Here we find that expression of the tetraspan-transmembrane protein CMTM5 (Chemokine-like factor-like MARVEL-transmembrane domain containing protein 5) is highly enriched in oligodendrocytes and CNS myelin. Genetic disruption of the Cmtm5-gene in oligodendrocytes of mice does not impair the development or ultrastructure of CNS myelin. However, oligodendroglial Cmtm5-deficiency causes an early-onset progressive axonopathy, which we also observe in global and in tamoxifen-induced oligodendroglial Cmtm5-mutants. Presence of the Wlds mutation ameliorates the axonopathy, implying a Wallerian degeneration-like pathomechanism. These results indicate that CMTM5 is involved in the function of oligodendrocytes to maintain axonal integrity rather than myelin biogenesis.

neuroscience↗

bioRxiv2021

Ire1α-Regulated Rate of mRNA Translation is Required for Acquisition of Identity and Polarity in Upper Layer Cortical Neurons

Evolutionary expansion of the neocortex is associated with the increase in upper layer neurons. Here, we present Inositol-Requiring Enzyme 1, Ire1, as an essential determinant of upper layer fate, neuronal polarization and cortical lamination. We demonstrate a non-canonical function of Ire1 in the regulation of global translation rates in the developing neocortex through its dynamic interaction with the ribosome and regulation of eIF4A1 and eEF-2 expression. Inactivation of Ire1 engenders lower protein synthesis rates associated with stalled ribosomes and decreased number of translation start sites. We show unique sensitivity of upper layer fate to translation rates. Whereas eEF-2 is required for cortical lamination, eIF4A1 regulates acquisition of upper layer fate downstream of Ire1 in a mechanism of translational control dependent on 5UTR-embedded structural elements in fate determinant genes. Our data unveil developmental regulation of ribosome dynamics as post-transcriptional mechanisms orchestrating neuronal diversity establishment and assembly of cortical layers. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/449563v2_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@115a09aorg.highwire.dtl.DTLVardef@e30d2dorg.highwire.dtl.DTLVardef@763b27org.highwire.dtl.DTLVardef@2586e9_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LISmall molecule screening reveals Ire1 upstream of upper layer neuronal identity C_LIO_LIPolarization and proper lamination of layer II/III neurons require Ire1 C_LIO_LIDevelopment of upper layers requires high translation rates driven by eIF4A1 and eEF-2 downstream of Ire1 C_LIO_LIeIF4A1-dependent Satb2 mRNA translation initiation is a mechanism of upper layer fate acquisition C_LI

neuroscience↗

bioRxiv2020

White matter integrity requires continuous myelin synthesis at the inner tongue

Myelin, the electrically insulating axonal sheath, is composed of lipids and proteins with exceptionally long lifetime. This raises the question how myelin function is affected by myelin turnover. We have studied the integrity of myelinated tracts after experimentally preventing the formation of new myelin in the CNS of adult mice, using an inducible Mbp null allele. Oligodendrocytes survived recombination, continued expressing myelin genes, but failed to maintain compacted myelin sheaths. Using 3D electron microscopy and mass spectrometry imaging we visualized myelin-like membranes that failed to incorporate adaxonally, most prominently at juxta-paranodes. Myelinoid body formation indicated degradation of existing myelin at the abaxonal side and at the inner tongue of the sheath. Compacted myelin thinning and shortening of internodes, with about 50% myelin lost after 20 weeks (=5 months), ultimately led to axonal pathology and neurological disease. These data reveal that functional axon-myelin units require the continuous incorporation of new myelin membranes.

neuroscience↗

bioRxiv2019

Physiological and pathophysiological homeostasis of astroglial channel proteins by Nedd4-2

Nedd4-2 is an E3 ubiquitin ligase, missense mutation of which is related to familial epilepsy, indicating its critical role in regulating neuronal network activity. However, Nedd4-2 substrates involved in neuronal network function have yet to be identified. Using mouse lines lacking Nedd4-1 and Nedd4-2, we identified astrocytic channel proteins inwardly rectifying K+ channel 4.1 (Kir4.1) and Connexin43 as Nedd4-2 substrates. We found that the expression of Kir4.1 and Connexin43 is increased upon conditional deletion of Nedd4-2 in astrocytes, leading to an elevation of astrocytic membrane ion permeability and gap junction activity, with a consequent reduction of {gamma}-oscillatory neuronal network activity. Interestingly, our biochemical data demonstrate that missense mutations found in familial epileptic patients produce gain-of-function of Nedd4-2 gene product. Our data reveal a process of coordinated astrocytic ion channel proteostasis that controls astrocyte function and astrocyte-dependent neuronal network activity, and elucidate a potential mechanism by which aberrant Nedd4-2 function leads to epilepsy.\n\nCONDENSED TITLEUbiquitination of Astrocytic Channels by Nedd4-2\n\nSUMMARYUbiquitination is a key regulatory machinery for protein expression. Our present work provides evidence that astrocytic ion channel proteostasis coordinated by an E3 ubiquitin ligase Nedd4-2 is of particular importance for the maintenance of neuronal network activity.

neuroscience↗

bioRxiv2019

The Kaufman oculocerebrofacial syndrome protein Ube3b regulates synapse number by ubiquitinating Ppp3cc.

Kaufman oculocerebrofacial syndrome (KOS) is a severe autosomal recessive disorder characterized by intellectual disability, developmental delays, microcephaly and characteristic dysmorphisms. Biallelic mutations of UBE3B, encoding for a ubiquitin ligase E3B are causative for KOS. In this report, we characterize neuronal functions of its murine ortholog Ube3b. We show that Ube3b regulates dendritic branching in a cell-autonomous manner. Moreover, Ube3b knockout (KO) neurons exhibit increased density and aberrant morphology of dendritic spines, altered synaptic physiology and changes in hippocampal circuit activity. Dorsal forebrain-specific Ube3b KO animals show impaired spatial learning and alterations in social interactions. We further demonstrate that Ube3b ubiquitinates the catalytic {gamma}-subunit of calcineurin (Ppp3cc), the overexpression of which phenocopies the loss of Ube3b with regard to dendritic spine density. This work provides insights into the molecular pathologies underlying intellectual disability-like phenotypes in a genetic mouse model for KOS.

neuroscience↗

bioRxiv2018

Complexin cooperates with Bruchpilot to tether synaptic vesicles to the active zone cytomatrix

Information processing by the nervous system depends on the release of neurotransmitter from synaptic vesicles (SVs) at the presynaptic active zone. Molecular components of the cytomatrix at the active zone (CAZ) regulate the final stages of the SV cycle preceding exocytosis and thereby shape the efficacy and plasticity of synaptic transmission. Part of this regulation is reflected by a physical association of SVs with filamentous CAZ structures. However, our understanding of the protein interactions underlying SV tethering by the CAZ is far from complete. The very C-terminal region of Bruchpilot (Brp), a key component of the Drosophila CAZ, participates in SV tethering. Yet so far, no vesicular or cytoplasmic molecules have been reported to engage in an interaction with Brps C-terminus. Here, we carried out an in vivo screen for molecules that link the Brp C-terminus to SVs. This strategy identified the conserved SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor) regulator Complexin (Cpx) as a vesicular interaction partner of Brp. We show that Brp and Cpx interact genetically and functionally. Interfering with Cpx targeting to SVs mirrored distinctive features of a C-terminal Brp truncation: impaired SV recruitment to the CAZ and enhanced short-term synaptic depression. Extending the study beyond Drosophila synapses, we interrogated active zones of mouse rod bipolar cells. Here, too, we collected evidence for an evolutionarily conserved role of Cpx upstream of SNARE complex assembly where it participates in SV tethering to the CAZ.

neuroscience↗