The IFT81-IFT74 complex acts as an unconventional RabL2 GTPase-activating protein during intraflagellar transport.
Cilium
GAP
GTPase
RabL2
intraflagellar transport
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
18 09 2023
18 09 2023
Historique:
revised:
24
07
2023
received:
04
06
2022
accepted:
03
08
2023
medline:
19
9
2023
pubmed:
22
8
2023
entrez:
22
8
2023
Statut:
ppublish
Résumé
Cilia are important cellular organelles for signaling and motility and are constructed via intraflagellar transport (IFT). RabL2 is a small GTPase that localizes to the basal body of cilia via an interaction with the centriolar protein CEP19 before downstream association with the IFT machinery, which is followed by initiation of IFT. We reconstituted and purified RabL2 with CEP19 or IFT proteins to show that a reconstituted pentameric IFT complex containing IFT81/74 enhances the GTP hydrolysis rate of RabL2. The binding site on IFT81/74 that promotes GTP hydrolysis in RabL2 was mapped to a 70-amino-acid-long coiled-coil region of IFT81/74. We present structural models for RabL2-containing IFT complexes that we validate in vitro and in cellulo and demonstrate that Chlamydomonas IFT81/74 enhances GTP hydrolysis of human RabL2, suggesting an ancient evolutionarily conserved activity. Our results provide an architectural understanding of how RabL2 is incorporated into the IFT complex and a molecular rationale for why RabL2 dissociates from anterograde IFT trains soon after departure from the ciliary base.
Identifiants
pubmed: 37606072
doi: 10.15252/embj.2022111807
pmc: PMC10505919
doi:
Substances chimiques
GTPase-Activating Proteins
0
Amino Acids
0
Guanosine Triphosphate
86-01-1
IFT81 protein, human
0
Muscle Proteins
0
IFT74 protein, human
0
Cytoskeletal Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e111807Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103639
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA225520
Pays : United States
Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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