NAB-1 instructs synapse assembly by linking adhesion molecules and F-actin to active zone proteins.
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.
Howard Hughes Medical Institute, Department of Biology, Stanford University, Stanford, California, USA.
Poh Hui
PH
Chia
Maulik R
MR
Patel
Kang
K
Shen
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007136:Immunoglobulins / Q000235:genetics / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D007814:Larva; D008164:Luminescent Proteins; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000166:cytology*; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D013569:Synapses / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism; D000099273:Neurabins
D000199:Actins; D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D036341:Intercellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D000099273:Neurabins; C468652:SYD-1 protein, C elegans; C490598:SYD-2 protein, C elegans; C473474:SYG-1 protein, C elegans