posted on 2016-04-05, 00:00authored byMaike 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.
Funding
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.