Dual clathrin and integrin signaling systems regulate growth factor receptor activation.
Cell Adhesion
/ physiology
Cell Line, Tumor
Cell Membrane
/ metabolism
Cell Movement
/ physiology
Cell Proliferation
/ physiology
Clathrin
/ chemistry
Clathrin-Coated Vesicles
/ metabolism
Endocytosis
ErbB Receptors
/ metabolism
GRB2 Adaptor Protein
/ metabolism
Humans
Integrin beta Chains
/ metabolism
Microscopy, Electron
Signal Transduction
/ physiology
src-Family Kinases
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 02 2022
16 02 2022
Historique:
received:
16
11
2020
accepted:
18
01
2022
entrez:
17
2
2022
pubmed:
18
2
2022
medline:
3
3
2022
Statut:
epublish
Résumé
The crosstalk between growth factor and adhesion receptors is key for cell growth and migration. In pathological settings, these receptors are drivers of cancer. Yet, how growth and adhesion signals are spatially organized and integrated is poorly understood. Here we use quantitative fluorescence and electron microscopy to reveal a mechanism where flat clathrin lattices partition and activate growth factor signals via a coordinated response that involves crosstalk between epidermal growth factor receptor (EGFR) and the adhesion receptor β5-integrin. We show that ligand-activated EGFR, Grb2, Src, and β5-integrin are captured by clathrin coated-structures at the plasma membrane. Clathrin structures dramatically grow in response to EGF into large flat plaques and provide a signaling platform that link EGFR and β5-integrin through Src-mediated phosphorylation. Disrupting this EGFR/Src/β5-integrin axis prevents both clathrin plaque growth and dampens receptor signaling. Our study reveals a reciprocal regulation between clathrin lattices and two different receptor systems to coordinate and enhance signaling. These findings have broad implications for the regulation of growth factor signaling, adhesion, and endocytosis.
Identifiants
pubmed: 35173166
doi: 10.1038/s41467-022-28373-x
pii: 10.1038/s41467-022-28373-x
pmc: PMC8850434
doi:
Substances chimiques
Clathrin
0
GRB2 Adaptor Protein
0
GRB2 protein, human
0
Integrin beta Chains
0
integrin beta5
0
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
src-Family Kinases
EC 2.7.10.2
Banques de données
figshare
['10.25444/nhlbi.17159351']
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
905Informations de copyright
© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
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