J Cell Biol-2013-Kittelmann-849-63.pdf (3.94 MB)
Liprin-alpha/SYD-2 determines the size of dense projections in presynaptic active zones in C. elegans
journal contributionposted on 2016-04-05, 00:00 authored by Maike Kittelmann, Jan Hegermann, Alexandr Goncharov, Hidenori Taru, Mark H. Ellisman, Janet E. Richmond, Yishi Jin, Stefan Eimer
Synaptic vesicle (SV) release is spatially and temporally regulated by a network of proteins that form the presynaptic active zone (AZ). The hallmark of most AZs is an electron-dense projection (DP) surrounded by SVs. Despite their importance for our understanding of triggered SV release, high-resolution analyses of DP structures are limited. Using electron microscopy, we show that DPs at Caenorhabditis elegans neuromuscular junctions (NMJs) were highly structured, composed of building units forming bays in which SVs are docked to the AZ membrane. Furthermore, larger ribbonlike DPs that were multimers of the NMJ building unit are found at synapses between inter- and motoneurons. We also demonstrate that DP size is determined by the activity of the AZ protein SYD-2/Liprin-α. Whereas loss of syd-2 function led to smaller DPs, syd-2 gain-of-function mutants displayed larger ribbonlike DPs through increased recruitment of ELKS-1/ELKS. Therefore, our data suggest that a main role of SYD-2/Liprin-α in synaptogenesis is to regulate the polymerization of DPs.
The NCMIR contributions for collection and reconstruction were supported by National Institutes of Health support under awards P41RR004050 and P41GM103412-24 to M.H. Ellisman. M. Kittelmann was supported by the Education Abroad Program Göttingen, the German–American Fulbright Program, and the Göttingen Graduate School for Neurosciences and Molecular Biosciences. J.E. Richmond was supported by an advanced career award of the Alexander von Humboldt Foundation. H. Taru was supported by a National Institutes of Health grant (NS035546) to Y. Jin and Grants-in-Aid for Scientific Research. A. Goncharov is an associate and Y. Jin is an investigator of the Howard Hughes Medical Institute.
Publisher Statement© 2013 Kittelmann et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc sa/3.0/).
PublisherRockefeller University Press