Nature Neuroscience
- 9, 1488 - 1498 (2006)
Published online: 19 November 2006; | doi:10.1038/nn1806
Hierarchical assembly of presynaptic components in defined C. elegans synapsesMaulik R Patel1, 2, Emily K Lehrman1, Vivian Y Poon1, 2, Justin G Crump3, Mei Zhen4, Cornelia I Bargmann5 & Kang Shen1, 21
Department of Biological Sciences, Stanford University, 385 Serra Mall, Stanford, California 94305, USA. 2
Neurosciences Program, Stanford University, 385 Serra Mall, Stanford, California 94305, USA. 3
Zilkha Neurogenetic Institute, University of Southern California, 1975 Zonal Avenue KAM-B16, Los Angeles, California 90089-9031. 4
Department of Medical Genetics and Microbiology, Samuel Lunenfeld Research Institute, University of Toronto, 600 University Avenue, Ontario M5G 1X5, Canada. 5
Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10021.
Correspondence should be addressed to Kang Shen kangshen@stanford.edu The presynaptic regions of axons accumulate synaptic vesicles, active zone proteins and periactive zone proteins. However, the rules for orderly recruitment of presynaptic components are not well understood. We systematically examined molecular mechanisms of presynaptic development in egg-laying synapses of Caenorhabditis elegans, demonstrating that two scaffolding molecules, SYD-1 and SYD-2, have key roles in presynaptic assembly. SYD-2 (liprin- ) was previously shown to regulate the size and the shape of active zones. We now show that in syd-1 and syd-2 mutants, synaptic vesicles and numerous other presynaptic proteins fail to accumulate at presynaptic sites. SYD-1 and SYD-2 function cell-autonomously at presynaptic terminals, downstream of synaptic specificity molecule SYG-1. SYD-1 is likely to act upstream of SYD-2 to positively regulate its synaptic assembly activity. These data imply a hierarchical organization of presynaptic assembly, in which transmembrane specificity molecules initiate synaptogenesis by recruiting a few key scaffolding proteins, which in turn assemble other presynaptic components.
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