TBC1D5-Catalyzed Cycling of Rab7 Is Required for Retromer-Mediated Human Papillomavirus Trafficking during Virus Entry.
Alphapapillomavirus
/ metabolism
Cell Line
GTPase-Activating Proteins
/ metabolism
HEK293 Cells
HeLa Cells
Humans
Keratinocytes
Papillomavirus Infections
/ metabolism
Protein Transport
Vesicular Transport Proteins
/ metabolism
Virus Internalization
rab GTP-Binding Proteins
/ metabolism
rab7 GTP-Binding Proteins
HPV
Rab7B
TBC1D5
functional genetics screen
proximity ligation assay
retrograde
retromer
senescence
traptamer
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
09 06 2020
09 06 2020
Historique:
received:
30
09
2019
revised:
16
04
2020
accepted:
18
05
2020
entrez:
11
6
2020
pubmed:
11
6
2020
medline:
20
5
2021
Statut:
ppublish
Résumé
During virus entry, human papillomaviruses are sorted by the cellular trafficking complex, called retromer, into the retrograde transport pathway to traffic from the endosome to downstream cellular compartments, but regulation of retromer activity during HPV entry is poorly understood. Here we selected artificial proteins that modulate cellular proteins required for HPV infection and discovered that entry requires TBC1D5, a retromer-associated, Rab7-specific GTPase-activating protein. Binding of retromer to the HPV L2 capsid protein recruits TBC1D5 to retromer at the endosome membrane, which then stimulates hydrolysis of Rab7-GTP to drive retromer disassembly from HPV and delivery of HPV to the retrograde pathway. Although the cellular retromer cargos CIMPR and DMT1-II require only GTP-bound Rab7 for trafficking, HPV trafficking requires cycling between GTP- and GDP-bound Rab7. Thus, ongoing cargo-induced membrane recruitment, assembly, and disassembly of retromer complexes drive HPV trafficking.
Identifiants
pubmed: 32521275
pii: S2211-1247(20)30730-0
doi: 10.1016/j.celrep.2020.107750
pmc: PMC7339955
mid: NIHMS1603430
pii:
doi:
Substances chimiques
GTPase-Activating Proteins
0
TBC1D5 protein, human
0
Vesicular Transport Proteins
0
rab7 GTP-Binding Proteins
0
rab7 GTP-binding proteins, human
0
rab GTP-Binding Proteins
EC 3.6.5.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
107750Subventions
Organisme : NCI NIH HHS
ID : P01 CA016038
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI102876
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA037157
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI055403
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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