title: The BH3-only SNARE BNip1 mediates photoreceptor apoptosis in response to vesicular fusion defects.
abstract: Intracellular vesicular transport is important for photoreceptor function and maintenance. However, the mechanism underlying photoreceptor degeneration in response to vesicular transport defects is unknown. Here, we report that photoreceptors undergo apoptosis in a zebrafish β-soluble N-ethylmaleimide-sensitive factor attachment protein (β-SNAP) mutant. β-SNAP cooperates with N-ethylmaleimide-sensitive factor to recycle the SNAP receptor (SNARE), a key component of the membrane fusion machinery, by disassembling the cis-SNARE complex generated in the vesicular fusion process. We found that photoreceptor apoptosis in the β-SNAP mutant was dependent on the BH3-only protein BNip1. BNip1 functions as a component of the syntaxin-18 SNARE complex and regulates retrograde transport from the Golgi to the endoplasmic reticulum. Failure to disassemble the syntaxin-18 cis-SNARE complex caused BNip1-dependent apoptosis. These data suggest that the syntaxin-18 cis-SNARE complex functions as an alarm factor that monitors vesicular fusion competence and that BNip1 transforms vesicular fusion defects into photoreceptor apoptosis.
authors.affiliation: Developmental Neurobiology Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna, Okinawa 904-0412, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nishiwaki
authors.forename: Asuka
authors.initials: A
authors.lastname: Yoshizawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kojima
authors.forename: Eri
authors.initials: E
authors.lastname: Oguri
authors.forename: Shohei
authors.initials: S
authors.lastname: Nakamura
authors.forename: Shohei
authors.initials: S
authors.lastname: Suzuki
authors.forename: Junichi
authors.initials: J
authors.lastname: Yuasa-Kawada
authors.forename: Mariko
authors.initials: M
authors.lastname: Kinoshita-Kawada
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Mochizuki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Masai
mesh_terms: D000818:Animals; D017209:Apoptosis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D008561:Membrane Fusion; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D055351:Retinal Neurons / Q000378:metabolism / Q000473:pathology; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D019253:Proto-Oncogene Proteins c-bcl-2; D050765:Qa-SNARE Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins