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

Siebert, M., Böhme, M. A., Driller, J. H., Babikir, H., Mampell, M. M., Rey, U., et al. (2015). A high affinity RIM-binding protein/Aplip1 interaction prevents the formation of ectopic axonal active zones. eLife, 4: e06935. doi:10.7554/eLife.06935.001.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-3A0F-1 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-2A28-4
Genre: Journal Article

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Siebert, M., Author
Böhme, M. A., Author
Driller, J. H., Author
Babikir, H., Author
Mampell, M. M., Author
Rey, U., Author
Ramesh, N., Author
Matkovic, T., Author
Holton, N., Author
Reddy-Alla, S., Author
Göttfert, F.1, Author              
Kamin, D.1, Author              
Quentin, C., Author
Klinedinst, S., Author
Andlauer, T. F., Author
Hell, S. W.1, Author              
Collins, C. A., Author
Wahl, M. C., Author
Loll, B., Author
Sigrist, S. J., Author
Affiliations:
1Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society, ou_578627              

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 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.

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Language(s): eng - English
 Dates: 2015-08-14
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.7554/eLife.06935.001
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Title: eLife
Source Genre: Journal
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Pages: 30 Volume / Issue: 4 Sequence Number: e06935 Start / End Page: - Identifier: -