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ECM-dependent regulation of septin 7 in focal adhesions promotes mechanosensing and functional response in fibroblasts

Sturgess, Wesley LU ; Packirisamy, Swathi LU orcid ; Geneidy, Rodina ; Nordenfelt, Pontus LU orcid and Swaminathan, Vinay LU orcid (2024) In iScience 27(12).
Abstract

Fibroblasts are adherent cells that maintain tissue homeostasis by sensing and responding to the extracellular matrix (ECM). Focal adhesions (FAs) link these ECM changes to actomyosin dynamics through changes in its composition, influencing cellular response. Septin-7 (Sept-7) has previously been found in FA proteomics studies and shown to influence ECM sensing. Using total internal reflection microscopy, we found that ECM-mediated integrin activation regulates spatially distinct Sept-7 structures in FAs. In perinuclear regions, ECM binding stabilized Sept-7 bundles at the back of FAs, while in the core of peripheral FAs high integrin activation promoted elongation of Sept-7 structures. Ventral Sept-7 structures were crucial for ECM... (More)

Fibroblasts are adherent cells that maintain tissue homeostasis by sensing and responding to the extracellular matrix (ECM). Focal adhesions (FAs) link these ECM changes to actomyosin dynamics through changes in its composition, influencing cellular response. Septin-7 (Sept-7) has previously been found in FA proteomics studies and shown to influence ECM sensing. Using total internal reflection microscopy, we found that ECM-mediated integrin activation regulates spatially distinct Sept-7 structures in FAs. In perinuclear regions, ECM binding stabilized Sept-7 bundles at the back of FAs, while in the core of peripheral FAs high integrin activation promoted elongation of Sept-7 structures. Ventral Sept-7 structures were crucial for ECM sensing, impacting region-specific FA elongation, stabilization, and contributing to fibroblast mechanosensitivity. Taken together, our results suggest that ECM and integrin-dependent regulation of ventral Sept-7 structures plays a pivotal role in fibroblast ECM sensing and mechanotransduction through its recruitment and assembly into FA subpopulations.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cell biology, Mechanobiology, Stem cells research
in
iScience
volume
27
issue
12
article number
111355
publisher
Elsevier
external identifiers
  • pmid:39650732
  • scopus:85209716486
ISSN
2589-0042
DOI
10.1016/j.isci.2024.111355
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2024 The Author(s)
id
a8239eab-dc5b-4695-8806-10fc084edc7c
date added to LUP
2025-01-08 15:50:52
date last changed
2025-07-10 07:24:18
@article{a8239eab-dc5b-4695-8806-10fc084edc7c,
  abstract     = {{<p>Fibroblasts are adherent cells that maintain tissue homeostasis by sensing and responding to the extracellular matrix (ECM). Focal adhesions (FAs) link these ECM changes to actomyosin dynamics through changes in its composition, influencing cellular response. Septin-7 (Sept-7) has previously been found in FA proteomics studies and shown to influence ECM sensing. Using total internal reflection microscopy, we found that ECM-mediated integrin activation regulates spatially distinct Sept-7 structures in FAs. In perinuclear regions, ECM binding stabilized Sept-7 bundles at the back of FAs, while in the core of peripheral FAs high integrin activation promoted elongation of Sept-7 structures. Ventral Sept-7 structures were crucial for ECM sensing, impacting region-specific FA elongation, stabilization, and contributing to fibroblast mechanosensitivity. Taken together, our results suggest that ECM and integrin-dependent regulation of ventral Sept-7 structures plays a pivotal role in fibroblast ECM sensing and mechanotransduction through its recruitment and assembly into FA subpopulations.</p>}},
  author       = {{Sturgess, Wesley and Packirisamy, Swathi and Geneidy, Rodina and Nordenfelt, Pontus and Swaminathan, Vinay}},
  issn         = {{2589-0042}},
  keywords     = {{Cell biology; Mechanobiology; Stem cells research}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{12}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{ECM-dependent regulation of septin 7 in focal adhesions promotes mechanosensing and functional response in fibroblasts}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2024.111355}},
  doi          = {{10.1016/j.isci.2024.111355}},
  volume       = {{27}},
  year         = {{2024}},
}