title: Myosin Va and Endoplasmic Reticulum Calcium Channel Complex Regulates Membrane Export during Axon Guidance.
abstract: During axon guidance, growth cones navigate toward attractive cues by inserting new membrane on the cue side. This process depends on Ca(2+) release from endoplasmic reticulum (ER) Ca(2+) channels, but the Ca(2+) sensor and effector governing this asymmetric vesicle export remain unknown. We identified a protein complex that controls asymmetric ER Ca(2+)-dependent membrane vesicle export. The Ca(2+)-dependent motor protein myosin Va (MyoVa) tethers membrane vesicles to the ER via a common binding site on the two major ER Ca(2+) channels, inositol 1,4,5-trisphosphate and ryanodine receptors. In response to attractive cues, micromolar Ca(2+) from ER channels triggers MyoVa-channel dissociation and the movement of freed vesicles to the cue side, enabling growth cone turning. MyoVa-Ca(2+) channel interactions are required for proper long-range axon growth in developing spinal cord in vivo. These findings reveal a peri-ER membrane export pathway for Ca(2+)-dependent attraction in axon guidance.
authors.affiliation: RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Wada
authors.affiliation: RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Nakata
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Tatsu
authors.affiliation: RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Ooashi
authors.affiliation: RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Tetsuko
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Nabetani
authors.affiliation: RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Electronic address: kamiguchi@brain.riken.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamiguchi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000071437:Axon Guidance; D001692:Biological Transport; D002118:Calcium; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling; D002462:Cell Membrane / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005089:Exocytosis; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D024701:Myosin Type V / Q000378:metabolism*; D011485:Protein Binding; D013116:Spinal Cord / Q000378:metabolism; D022161:Transport Vesicles; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D050988:Vesicle-Associated Membrane Protein 2; C494808:vesicle-associated membrane protein 2, mouse; D024701:Myosin Type V; D002118:Calcium