A high affinity RIM-binding protein/Aplip1 interaction prevents the formation of ectopic axonal active zones

作者：Siebert Matthias; Boehme Mathias A; Driller Jan H; Babikir Husam; Mampell Malou M; Rey Ulises; Ramesh Niraja; Matkovic Tanja; Holton Nicole; Reddy Alla Suneel; Goettfert Fabian; Kamin Dirk; Quentin Christine; Klinedinst Susan; Andlauer Till F M; Hell Stefan W; Collins Catherine A; Wahl Markus C; Loll Bernhard; Sigrist Stephan J^*

来源：eLife, 2015, 4: e06935.

DOI：10.7554/eLife.06935

Synaptic vesicles (SVs) fuse at active zones (AZs) covered by a protein scaffold, at Drosophila synapses comprised of ELKS family member Bruchpilot (BRP) and RIM-binding protein (RBP). We here demonstrate axonal co-transport of BRP and RBP using intravital live imaging, with both proteins co-accumulating in axonal aggregates of several transport mutants. RBP, via its C-terminal Src-homology 3 (SH3) domains, binds Aplip1/JIP1, a transport adaptor involved in kinesin-dependent SV transport. We show in atomic detail that RBP C-terminal SH3 domains bind a proline-rich (PxxP) motif of Aplip1/JIP1 with submicromolar affinity. Pointmutating this PxxP motif provoked formation of ectopic AZ-like structures at axonal membranes. Direct interactions between AZ proteins and transport adaptors seem to provide complex avidity and shield synaptic interaction surfaces of pre-assembled scaffold protein transport complexes, thus, favouring physiological synaptic AZ assembly over premature assembly at axonal membranes.

• 出版日期2015-8-14