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Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression
by
Wills, Jimi C.
, Armstrong, J. Douglas
, Bickmore, Wendy A.
, Loftus, Alexander E. P.
, Parsons, Maddy
, Griffith, Billie G. C.
, von Kriegsheim, Alex
, Beernaert, Bruno
, Frame, Margaret C.
, Lee, Martin
, Leigh, Irene M.
, Byron, Adam
, Wheeler, Ann P.
, Valli, Jessica
, Li Mow Chee, Frederic
, Kumar, Yatendra
, Proby, Charlotte M.
in
13/106
/ 14/19
/ 14/35
/ 38
/ 38/23
/ 38/39
/ 38/77
/ 631/80/128
/ 631/80/386
/ 631/80/79
/ 82/58
/ 96/95
/ Actin
/ Actins - genetics
/ Actins - metabolism
/ Adhesion
/ Carcinoma, Squamous Cell - metabolism
/ Cell Nucleus - metabolism
/ Chromatin
/ CRISPR
/ Cytoskeleton
/ Depletion
/ Extracellular matrix
/ Gene Expression
/ Humanities and Social Sciences
/ Humans
/ Immunomodulation
/ Integrins - metabolism
/ Kinases
/ Membrane proteins
/ Membranes
/ Microfilament Proteins - metabolism
/ multidisciplinary
/ Nuclear Envelope - metabolism
/ Nuclear Lamina - metabolism
/ Phosphorylation
/ Proteins
/ Science
/ Science (multidisciplinary)
/ Signal transduction
/ Signaling
/ Skin Neoplasms - metabolism
/ Squamous cell carcinoma
/ Tyrosine
2023
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Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression
by
Wills, Jimi C.
, Armstrong, J. Douglas
, Bickmore, Wendy A.
, Loftus, Alexander E. P.
, Parsons, Maddy
, Griffith, Billie G. C.
, von Kriegsheim, Alex
, Beernaert, Bruno
, Frame, Margaret C.
, Lee, Martin
, Leigh, Irene M.
, Byron, Adam
, Wheeler, Ann P.
, Valli, Jessica
, Li Mow Chee, Frederic
, Kumar, Yatendra
, Proby, Charlotte M.
in
13/106
/ 14/19
/ 14/35
/ 38
/ 38/23
/ 38/39
/ 38/77
/ 631/80/128
/ 631/80/386
/ 631/80/79
/ 82/58
/ 96/95
/ Actin
/ Actins - genetics
/ Actins - metabolism
/ Adhesion
/ Carcinoma, Squamous Cell - metabolism
/ Cell Nucleus - metabolism
/ Chromatin
/ CRISPR
/ Cytoskeleton
/ Depletion
/ Extracellular matrix
/ Gene Expression
/ Humanities and Social Sciences
/ Humans
/ Immunomodulation
/ Integrins - metabolism
/ Kinases
/ Membrane proteins
/ Membranes
/ Microfilament Proteins - metabolism
/ multidisciplinary
/ Nuclear Envelope - metabolism
/ Nuclear Lamina - metabolism
/ Phosphorylation
/ Proteins
/ Science
/ Science (multidisciplinary)
/ Signal transduction
/ Signaling
/ Skin Neoplasms - metabolism
/ Squamous cell carcinoma
/ Tyrosine
2023
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Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression
by
Wills, Jimi C.
, Armstrong, J. Douglas
, Bickmore, Wendy A.
, Loftus, Alexander E. P.
, Parsons, Maddy
, Griffith, Billie G. C.
, von Kriegsheim, Alex
, Beernaert, Bruno
, Frame, Margaret C.
, Lee, Martin
, Leigh, Irene M.
, Byron, Adam
, Wheeler, Ann P.
, Valli, Jessica
, Li Mow Chee, Frederic
, Kumar, Yatendra
, Proby, Charlotte M.
in
13/106
/ 14/19
/ 14/35
/ 38
/ 38/23
/ 38/39
/ 38/77
/ 631/80/128
/ 631/80/386
/ 631/80/79
/ 82/58
/ 96/95
/ Actin
/ Actins - genetics
/ Actins - metabolism
/ Adhesion
/ Carcinoma, Squamous Cell - metabolism
/ Cell Nucleus - metabolism
/ Chromatin
/ CRISPR
/ Cytoskeleton
/ Depletion
/ Extracellular matrix
/ Gene Expression
/ Humanities and Social Sciences
/ Humans
/ Immunomodulation
/ Integrins - metabolism
/ Kinases
/ Membrane proteins
/ Membranes
/ Microfilament Proteins - metabolism
/ multidisciplinary
/ Nuclear Envelope - metabolism
/ Nuclear Lamina - metabolism
/ Phosphorylation
/ Proteins
/ Science
/ Science (multidisciplinary)
/ Signal transduction
/ Signaling
/ Skin Neoplasms - metabolism
/ Squamous cell carcinoma
/ Tyrosine
2023
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Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression
Journal Article
Mena regulates nesprin-2 to control actin–nuclear lamina associations, trans-nuclear membrane signalling and gene expression
2023
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Overview
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.
Cells transmit mechanical force to the nucleus via the cytoskeleton. Here, the authors reveal a role for the actin regulator Mena in force transmission at the nuclear envelope, where it regulates nuclear architecture, chromatin organization and gene expression.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/19
/ 14/35
/ 38
/ 38/23
/ 38/39
/ 38/77
/ 82/58
/ 96/95
/ Actin
/ Adhesion
/ Carcinoma, Squamous Cell - metabolism
/ CRISPR
/ Humanities and Social Sciences
/ Humans
/ Kinases
/ Microfilament Proteins - metabolism
/ Nuclear Envelope - metabolism
/ Proteins
/ Science
/ Tyrosine
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