Mena regulates nesprin-2 to control actin-nuclear lamina associations, trans-nuclear membrane signalling and gene expression.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 03 2023
23 03 2023
Historique:
received:
25
09
2020
accepted:
21
02
2023
entrez:
24
3
2023
pubmed:
25
3
2023
medline:
28
3
2023
Statut:
epublish
Résumé
Interactions between cells and the extracellular matrix, mediated by integrin adhesion complexes, play key roles in fundamental cellular processes, including the sensing and transduction of mechanical cues. Here, we investigate systems-level changes in the integrin adhesome in patient-derived cutaneous squamous cell carcinoma cells and identify the actin regulatory protein Mena as a key node in the adhesion complex network. Mena is connected within a subnetwork of actin-binding proteins to the LINC complex component nesprin-2, with which it interacts and co-localises at the nuclear envelope. Moreover, Mena potentiates the interactions of nesprin-2 with the actin cytoskeleton and the nuclear lamina. CRISPR-mediated Mena depletion causes altered nuclear morphology, reduces tyrosine phosphorylation of the nuclear membrane protein emerin and downregulates expression of the immunomodulatory gene PTX3 via the recruitment of its enhancer to the nuclear periphery. We uncover an unexpected role for Mena at the nuclear membrane, where it controls nuclear architecture, chromatin repositioning and gene expression. Our findings identify an adhesion protein that regulates gene transcription via direct signalling across the nuclear envelope.
Identifiants
pubmed: 36959177
doi: 10.1038/s41467-023-37021-x
pii: 10.1038/s41467-023-37021-x
pmc: PMC10036544
doi:
Substances chimiques
Actins
0
Integrins
0
Microfilament Proteins
0
Enah protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1602Subventions
Organisme : Medical Research Council
ID : MC_UU_00007/2
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A13044
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C157/A24837
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R008264/1
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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