Synaptojanin cooperates in vivo with endophilin through an unexpected mechanism.
Synaptojanin and endophilin represent a classic pair of endocytic proteins that exhibit coordinated action during rapid synaptic vesicle endocytosis. Current models suggest that synaptojanin activity is tightly associated with endophilin through high-affinity binding between the synaptojanin proline-rich domain (PRD) and the endophilin SH3 domain. Surprisingly, we find that truncated synaptojanin lacking the PRD domain sustains normal synaptic transmission, indicating that synaptojanin's core function in vivo resides in the remaining two domains that contain phosphoinositide-phosphatase activities: an N-terminal Sac1 phosphatase domain and a 5-phosphatase domain. We further show that the Sac1 domain plays an unexpected role in targeting synaptojanin to synapses. The requirement for Sac1 is bypassed by tethering the synaptojanin 5-phophatase to the endophilin membrane-bending Bin-Amphiphysin-Rvs (BAR) domain. Together, our results uncover an unexpected role for the Sac1 domain in vivo in supporting coincident action between synaptojanin and endophilin at synapses.
Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States.
Yongming
Y
Dong
College of Life Science, Sichuan University, Chengdu, China.
Yueyang
Y
Gou
College of Life Science, Sichuan University, Chengdu, China.
Yi
Y
Li
Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States.
Yan
Y
Liu
Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States.
Jihong
J
Bai
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D004268:DNA-Binding Proteins / Q000235:genetics; D004705:Endocytosis / Q000235:genetics*; D018014:Gene Transfer Techniques; D008845:Microinjections; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D013569:Synapses / Q000235:genetics*; D009435:Synaptic Transmission / Q000235:genetics* / Q000502:physiology; D019895:Transposases / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C111652:mariner transposases; D019895:Transposases; C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases
C. elegans; Sac1 phosphatase domain; cell biology; endocytosis; endophilin; neuroscience; synaptic transmission; synaptojanin