scholarly journals Author response: A high affinity RIM-binding protein/Aplip1 interaction prevents the formation of ectopic axonal active zones

2015 ◽  
Author(s):  
Matthias Siebert ◽  
Mathias A Böhme ◽  
Jan H Driller ◽  
Husam Babikir ◽  
Malou M Mampell ◽  
...  
Keyword(s):  
Binding Protein ◽  
Author Response ◽  
High Affinity ◽  
Active Zones

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

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Matthias Siebert ◽  
Mathias A Böhme ◽  
Jan H Driller ◽  
Husam Babikir ◽  
Malou M Mampell ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Protein Transport ◽  
Binding Protein ◽  
Sh3 Domains ◽  
Src Homology 3 ◽  
High Affinity ◽  
Pxxp Motif ◽  
Transport Mutants ◽  
Src Homology ◽  
Active Zones

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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