RRC ID 46049
Author Chia PH, Patel MR, Shen K.
Title NAB-1 instructs synapse assembly by linking adhesion molecules and F-actin to active zone proteins.
Journal Nat Neurosci
Abstract During synaptogenesis, macromolecular protein complexes assemble at the pre- and postsynaptic membrane. Extensive literature identifies many transmembrane molecules sufficient to induce synapse formation and several intracellular scaffolding molecules responsible for assembling active zones and recruiting synaptic vesicles. However, little is known about the molecular mechanisms coupling membrane receptors to active zone molecules during development. Using Caenorhabditis elegans, we identify an F-actin network present at nascent presynaptic terminals and required for presynaptic assembly. We unravel a sequence of events whereby specificity-determining adhesion molecules define the location of developing synapses and locally assemble F-actin. Next, the adaptor protein NAB-1 (neurabin) binds to F-actin and recruits active zone proteins SYD-1 and SYD-2 (liprin-α) by forming a tripartite complex. NAB-1 localizes transiently to synapses during development and is required for presynaptic assembly. Altogether, we identify a role for the actin cytoskeleton during presynaptic development and characterize a molecular pathway whereby NAB-1 links synaptic partner recognition to active zone assembly.
Volume 15(2)
Pages 234-42
Published 2012-1-8
DOI 10.1038/nn.2991
PII nn.2991
PMID 22231427
PMC PMC3848868
MeSH Actins / genetics Actins / metabolism* Animals Animals, Genetically Modified Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology* Cell Adhesion Molecules / genetics Cell Adhesion Molecules / metabolism* Cell Movement / genetics Gene Expression Regulation, Developmental / genetics Immunoglobulins / genetics Immunoglobulins / physiology* Intercellular Signaling Peptides and Proteins Larva Luminescent Proteins Microfilament Proteins / genetics Microfilament Proteins / metabolism* Motor Neurons / cytology* Mutation / genetics Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Phosphoproteins / genetics Phosphoproteins / metabolism Presynaptic Terminals / metabolism Protein Transport / genetics Synapses / metabolism* Synaptic Vesicles / genetics Synaptic Vesicles / metabolism
IF 20.071
Times Cited 49
C.elegans tm1233