Human FCHO1 deficiency reveals role for clathrin-mediated endocytosis in development and function of T cells.
Animals
CD4-Positive T-Lymphocytes
/ pathology
Cell Differentiation
Cells, Cultured
Endocytosis
/ physiology
Female
HIV Infections
/ genetics
HIV-1
/ pathogenicity
Humans
Jurkat Cells
Loss of Function Mutation
Lymphopenia
/ genetics
Male
Membrane Proteins
/ chemistry
Mice
Pedigree
Receptors, Antigen, T-Cell
/ metabolism
T-Lymphocytes
/ physiology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 02 2020
25 02 2020
Historique:
received:
14
01
2019
accepted:
23
01
2020
entrez:
27
2
2020
pubmed:
27
2
2020
medline:
23
5
2020
Statut:
epublish
Résumé
Clathrin-mediated endocytosis (CME) is critical for internalisation of molecules across cell membranes. The FCH domain only 1 (FCHO1) protein is key molecule involved in the early stages of CME formation. The consequences of mutations in FCHO1 in humans were unknown. We identify ten unrelated patients with variable T and B cell lymphopenia, who are homozygous for six distinct mutations in FCHO1. We demonstrate that these mutations either lead to mislocalisation of the protein or prevent its interaction with binding partners. Live-cell imaging of cells expressing mutant variants of FCHO1 provide evidence of impaired formation of clathrin coated pits (CCP). Patient T cells are unresponsive to T cell receptor (TCR) triggering. Internalisation of the TCR receptor is severely perturbed in FCHO1-deficient Jurkat T cells but can be rescued by expression of wild-type FCHO1. Thus, we discovered a previously unrecognised critical role of FCHO1 and CME during T-cell development and function in humans.
Identifiants
pubmed: 32098969
doi: 10.1038/s41467-020-14809-9
pii: 10.1038/s41467-020-14809-9
pmc: PMC7042371
doi:
Substances chimiques
FCHO1 protein, human
0
Membrane Proteins
0
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1031Commentaires et corrections
Type : ErratumIn
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