title: RIM promotes calcium channel accumulation at active zones of the Drosophila neuromuscular junction.
abstract: 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.
authors.affiliation: Department of Biology and Neuroscience Program, Amherst College, Amherst, Massachusetts 01002, USA.
authors.forename: Ethan R
authors.initials: ER
authors.lastname: Graf
authors.forename: Vera
authors.initials: V
authors.lastname: Valakh
authors.forename: Christina M
authors.initials: CM
authors.lastname: Wright
authors.forename: Chunlai
authors.initials: C
authors.lastname: Wu
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Liu
authors.forename: Yong Q
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Aaron
authors.initials: A
authors.lastname: DiAntonio
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007814:Larva; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009469:Neuromuscular Junction / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D020692:rab3 GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology
chemical_list: C510146:BRP protein, Drosophila; D015220:Calcium Channels; D018076:DNA, Complementary; D029721:Drosophila Proteins; C577877:RIM protein, Drosophila; D020692:rab3 GTP-Binding Proteins