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Endosome maturation factors Rabenosyn-5/VPS45 and caveolin-1 regulate ciliary membrane and polycystin-2 homeostasis.

EMBO J.2018 May 02;37(9). Epub 2018 Mar 23
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摘要


Primary cilium structure and function relies on control of ciliary membrane homeostasis, regulated by membrane trafficking processes that deliver and retrieve ciliary components at the periciliary membrane. However, the molecular mechanisms controlling ciliary membrane establishment and maintenance, especially in relation to endocytosis, remain poorly understood. Here, using Caenorhabditis elegans, we describe closely linked functions for early endosome (EE) maturation factors RABS-5 (Rabenosyn-5) and VPS-45 (VPS45) in regulating cilium length and morphology, ciliary and periciliary membrane volume, and ciliary signalling-related sensory behaviour. We demonstrate that RABS-5 and VPS-45 control periciliary vesicle number and levels of select EE/endocytic markers (WDFY-2, CAV-1) and the ciliopathy membrane receptor PKD-2 (polycystin-2). Moreover, we show that CAV-1 (caveolin-1) also controls PKD-2 ciliary levels and associated sensory behaviour. These data link RABS-5 and VPS-45 ciliary functions to the processing of periciliary-derived endocytic vesicles and regulation of ciliary membrane homeostasis. Our findings also provide insight into the regulation of PKD-2 ciliary levels via integrated endosomal sorting and CAV-1-mediated endocytosis.

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