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Elife. 2015 Aug 14;4. doi: 10.7554/eLife.06935.

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

Author information

1
Institute for Biology/Genetics, Freie Universität Berlin, Berlin, Germany.
2
Institute of Chemistry and Biochemisty/Structural Biochemistry, Freie Universität Berlin, Berlin, Germany.
3
Department of Nanobiophotonics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
4
Department of Molecular Cellular and Developmental Biology, University of Michigan, Ann Arbor, United States.

Abstract

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.

KEYWORDS:

AZ scaffold proteins; D. melanogaster; active zone; axonal transport; neuroscience; synapses; transport adaptor

PMID:
26274777
PMCID:
PMC4536467
DOI:
10.7554/eLife.06935
[Indexed for MEDLINE]
Free PMC Article

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