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

eLife

Tanja Matkovic¹  Jan H Driller²  Bernhard Loll³  Stefan W Hell³  Markus C Wahl⁴  Christine Quentin⁴  Susan Klinedinst⁴  Niraja Ramesh⁵  Mathias A Böhme⁵  Malou M Mampell⁵  Dirk Kamin⁵  Till FM Andlauer⁵  Ulises Rey⁵  Nicole Holton⁵  Matthias Siebert⁵  Suneel Reddy-Alla⁵  Catherine A Collins⁵  Husam Babikir⁶  Fabian Göttfert⁶  Stephan J Sigrist⁶ 

[1] Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany;NeuroCure, Charité-Universitätsmedizin Berlin, Berlin, Germany;Department of Molecular Cellular and Developmental Biology, University of Michigan, Ann Arbor, United States;Department of Nanobiophotonics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany;Institute for Biology/Genetics, Freie Universität Berlin, Berlin, Germany;Institute of Chemistry and Biochemisty/Structural Biochemistry, Freie Universität Berlin, Berlin, Germany;

关键词: synapse;    axonal transport;    AZ scaffold protein;    transport adaptor;    active zone;   

DOI  :  10.7554/eLife.06935

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown