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Unraveling the intricate cargo-BBSome coupling mechanism at the ciliary tip.
Liu, Yan-Xia; Li, Wen-Juan; Zhang, Rui-Kai; Sun, Sheng-Nan; Fan, Zhen-Chuan.
Afiliación
  • Liu YX; State Key Laboratory of Food Nutrition and Safety, Institute of Health Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
  • Li WJ; State Key Laboratory of Food Nutrition and Safety, Institute of Health Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
  • Zhang RK; State Key Laboratory of Food Nutrition and Safety, Institute of Health Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
  • Sun SN; State Key Laboratory of Food Nutrition and Safety, Institute of Health Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
  • Fan ZC; State Key Laboratory of Food Nutrition and Safety, Institute of Health Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
Proc Natl Acad Sci U S A ; 120(13): e2218819120, 2023 03 28.
Article en En | MEDLINE | ID: mdl-36943875
ABSTRACT
Certain ciliary transmembrane and membrane-tethered signaling proteins migrate from the ciliary tip to base via retrograde intraflagellar transport (IFT), essential for maintaining their ciliary dynamics to enable cells to sense and transduce extracellular stimuli inside the cell. During this process, the BBSome functions as an adaptor between retrograde IFT trains and these signaling protein cargoes. The Arf-like 13 (ARL13) small GTPase resembles ARL6/BBS3 in facilitating these signaling cargoes to couple with the BBSome at the ciliary tip prior to loading onto retrograde IFT trains for transporting towards the ciliary base, while the molecular basis for how this intricate coupling event happens remains elusive. Here, we report that Chlamydomonas ARL13 only in a GTP-bound form (ARL13GTP) anchors to the membrane for diffusing into cilia. Upon entering cilia, ARL13 undergoes GTPase cycle for shuttling between the ciliary membrane (ARL13GTP) and matrix (ARL13GDP). To achieve this goal, the ciliary membrane-anchored BBS3GTP binds the ciliary matrix-residing ARL13GDP to activate the latter as an ARL13 guanine nucleotide exchange factor. At the ciliary tip, ARL13GTP recruits the ciliary matrix-residing and post-remodeled BBSome as an ARL13 effector to anchor to the ciliary membrane. This makes the BBSome spatiotemporally become available for the ciliary membrane-tethered phospholipase D (PLD) to couple with. Afterward, ARL13GTP hydrolyzes GTP for releasing the PLD-laden BBSome to load onto retrograde IFT trains. According to this model, hedgehog signaling defects associated with ARL13b and BBS3 mutations in humans could be satisfactorily explained, providing us a mechanistic understanding behind BBSome-cargo coupling required for proper ciliary signaling.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Cilios / Síndrome de Bardet-Biedl Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Año: 2023 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Cilios / Síndrome de Bardet-Biedl Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Año: 2023 Tipo del documento: Article