Planar Cell Polarity Effector Proteins Inturned and Fuzzy Form a Rab23 GEF Complex.
C-plane
Carpenter syndrome
Fuzzy
Inturned
Rab23
cilia
guanine nucleotide exchange factor
longin domain
planar polarity
primary cilium
Journal
Current biology : CB
ISSN: 1879-0445
Titre abrégé: Curr Biol
Pays: England
ID NLM: 9107782
Informations de publication
Date de publication:
07 10 2019
07 10 2019
Historique:
received:
27
06
2019
revised:
26
07
2019
accepted:
31
07
2019
pubmed:
1
10
2019
medline:
15
8
2020
entrez:
1
10
2019
Statut:
ppublish
Résumé
A subset of Rab GTPases have been implicated in cilium formation in cultured mammalian cells [1-6]. Rab11 and Rab8, together with their GDP-GTP exchange factors (GEFs), TRAPP-II and Rabin8, promote recruitment of the ciliary vesicle to the mother centriole and its subsequent maturation, docking, and fusion with the cell surface [2-5]. Rab23 has been linked to cilium formation and membrane trafficking at mature cilia [1, 7, 8]; however, the identity of the GEF pathway activating Rab23, a member of the Rab7 subfamily of Rabs, remains unclear. Longin-domain-containing complexes have been shown to act as GEFs for Rab7 subfamily GTPases [9-12]. Here, we show that Inturned and Fuzzy, proteins previously implicated as planar cell polarity (PCP) effectors and in developmentally regulated cilium formation [13, 14], contain multiple longin domains characteristic of the Mon1-Ccz1 family of Rab7 GEFs and form a specific Rab23 GEF complex. In flies, loss of Rab23 function gave rise to defects in planar-polarized trichome formation consistent with this biochemical relationship. In cultured human and mouse cells, Inturned and Fuzzy localized to the basal body and proximal region of cilia, and cilium formation was compromised by depletion of either Inturned or Fuzzy. Cilium formation arrested after docking of the ciliary vesicle to the mother centriole but prior to axoneme elongation and fusion of the ciliary vesicle and plasma membrane. These findings extend the family of longin domain GEFs and define a molecular activity linking Rab23-regulated membrane traffic to cilia and planar cell polarity.
Identifiants
pubmed: 31564489
pii: S0960-9822(19)31016-4
doi: 10.1016/j.cub.2019.07.090
pmc: PMC6864590
pii:
doi:
Substances chimiques
Drosophila Proteins
0
Membrane Proteins
0
Rab23 protein, Drosophila
0
Vesicular Transport Proteins
0
fy protein, Drosophila
0
in protein, Drosophila
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3323-3330.e8Subventions
Organisme : Medical Research Council
ID : MR/K018019/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P000177/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/N000420/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 097769/Z/11/Z
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M011801
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/P003818/1
Pays : United Kingdom
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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