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

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,...

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Bibliographic Details
Published in:The EMBO journal 2018-05, Vol.37 (9), p.n/a
Main Authors: Scheidel, Noémie, Kennedy, Julie, Blacque, Oliver E
Format: Article
Language:English
Subjects:
Animals
Caenorhabditis elegans
Caenorhabditis elegans - genetics
Caenorhabditis elegans - metabolism
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - metabolism
Caveolin
Caveolin 1 - genetics
Caveolin 1 - metabolism
caveolin‐1
Cell Membrane - genetics
Cell Membrane - metabolism
cilia
Cilia - genetics
Cilia - metabolism
Control
Endocytosis
Homeostasis
Markers
Mating behavior
Maturation
Membrane trafficking
Molecular modelling
Nematodes
PKD2
Rabenosyn‐5
Signaling
Structure-function relationships
TRPP Cation Channels - genetics
TRPP Cation Channels - metabolism
Vesicular Transport Proteins - genetics
Vesicular Transport Proteins - metabolism
VPS45
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Summary: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. Synopsis Sensory and developmental signaling events at the ciliary membrane regulate tissue formation and are disrupted in human ciliopathy disorders. Caenorhabditis elegans endosome maturation factors Rabenosyn‐5 (RABS‐5) and VPS‐45 regulate ciliary and peri‐ciliary membrane homeostasis, and, together with caveolin‐1 (CAV‐1), control the ciliary levels of polycystin‐2 (PKD‐2). Loss of C. elegans RABS‐5 and VPS‐45 causes defects in cilium structure and function, including ciliary and peri‐ciliary membrane expansions. RABS‐5 and VPS‐45 control peri‐ciliary vesicle number and levels of CAV‐1 and other endocytic markers near the ciliary base. RABS‐5, VPS‐45 and CAV‐1 control endosomal sorting of ciliary PKD‐2. RABS‐5, VPS‐45 and CAV‐1 are required for PKD‐2‐mediated male mating sensory behaviour. Endosomal uptake and sorting affect male mating behaviour in Caenorhabditis elegans by regulating ciliary membrane dynamics and the localization of polycystic kidney disease‐associated factor polycystin‐2 in sensory cilia.
ISSN:0261-4189
1460-2075
DOI:10.15252/embj.201798248