Regulation of synaptic transmission by RAB-3 and RAB-27 in Caenorhabditis elegans.
Rab small GTPases are involved in the transport of vesicles between different membranous organelles. RAB-3 is an exocytic Rab that plays a modulatory role in synaptic transmission. Unexpectedly, mutations in the Caenorhabditis elegans RAB-3 exchange factor homologue, aex-3, cause a more severe synaptic transmission defect as well as a defecation defect not seen in rab-3 mutants. We hypothesized that AEX-3 may regulate a second Rab that regulates these processes with RAB-3. We found that AEX-3 regulates another exocytic Rab, RAB-27. Here, we show that C. elegans RAB-27 is localized to synapse-rich regions pan-neuronally and is also expressed in intestinal cells. We identify aex-6 alleles as containing mutations in rab-27. Interestingly, aex-6 mutants exhibit the same defecation defect as aex-3 mutants. aex-6; rab-3 double mutants have behavioral and pharmacological defects similar to aex-3 mutants. In addition, we demonstrate that RBF-1 (rabphilin) is an effector of RAB-27. Therefore, our work demonstrates that AEX-3 regulates both RAB-3 and RAB-27, that both RAB-3 and RAB-27 regulate synaptic transmission, and that RAB-27 potentially acts through its effector RBF-1 to promote soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) function.
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Timothy R
TR
Mahoney
Qiang
Q
Liu
Takashi
T
Itoh
Shuo
S
Luo
Gayla
G
Hadwiger
Rose
R
Vincent
Zhao-Wen
ZW
Wang
Mitsunori
M
Fukuda
Michael L
ML
Nonet
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D017931:DNA Primers; D049452:Green Fluorescent Proteins / Q000235:genetics; D006160:Guanosine Triphosphate / Q000378:metabolism; D009154:Mutation; D011401:Promoter Regions, Genetic; D050600:SNARE Proteins / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D020692:rab3 GTP-Binding Proteins / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D050600:SNARE Proteins; D049452:Green Fluorescent Proteins; D006160:Guanosine Triphosphate; D020691:rab GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins