RIM promotes calcium channel accumulation at active zones of the Drosophila neuromuscular junction

Ethan R. Graf, Vera Valakh, Christina M. Wright, Chunlai Wu, Zhihua Liu, Yong Q. Zhang, Aaron DiAntonio

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Synaptic communication requires the controlled release of synaptic vesicles from presynaptic axon terminals. Release efficacy is regulated by the many proteins that comprise the presynaptic release apparatus, including Ca 2+ channels and proteins that influence Ca 2+ channel accumulation at release sites. Here we identify Drosophila RIM (Rab3 interacting molecule) and demonstrate that it localizes to active zones at the larval neuromuscular junction. In Drosophila RIM mutants, there is a large decrease in evoked synaptic transmission because of a significant reduction in both the clustering of Ca 2+ channels and the size of the readily releasable pool of synaptic vesicles at active zones. Hence, RIM plays an evolutionarily conserved role in regulating synaptic calcium channel localization and readily releasable pool size. Because RIM has traditionally been studied as an effector of Rab3 function, we investigate whether RIM is involved in the newly identified function of Rab3 in the distribution of presynaptic release machinery components across release sites. Bruchpilot (Brp), an essential component of the active zone cytomatrix T bar, is unaffected by RIM disruption, indicating that Brp localization and distribution across active zones does not require wild-type RIM. In addition, larvae containing mutations in both RIM and rab3 have reduced Ca 2+ channel levels and a Brp distribution that is very similar to that of the rab3 single mutant, indicating that RIM functions to regulate Ca 2+ channel accumulation but is not a Rab3 effector for release machinery distribution across release sites.

Original languageEnglish
Pages (from-to)16586-16596
Number of pages11
JournalJournal of Neuroscience
Issue number47
StatePublished - Nov 21 2012


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