دورية أكاديمية
Lfc subcellular localization and activity is controlled by αv-class integrin.
| العنوان: | Lfc subcellular localization and activity is controlled by αv-class integrin. |
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| المؤلفون: | Coló GP; Department of Molecular Medicine, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152, Martinsried, Germany., Seiwert A; Department of Molecular Medicine, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152, Martinsried, Germany., Haga RB; Department of Molecular Medicine, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152, Martinsried, Germany. |
| المصدر: | Journal of cell science [J Cell Sci] 2023 May 01; Vol. 136 (9). Date of Electronic Publication: 2023 May 01. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Company of Biologists Country of Publication: England NLM ID: 0052457 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-9137 (Electronic) Linking ISSN: 00219533 NLM ISO Abbreviation: J Cell Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge : Company of Biologists Original Publication: London. |
| مواضيع طبية MeSH: | Integrin alphaV*/metabolism , Integrin alpha5beta1*/metabolism, Humans ; Integrins/metabolism ; Guanine Nucleotide Exchange Factors/metabolism ; Phosphorylation ; rhoA GTP-Binding Protein/metabolism ; Rho Guanine Nucleotide Exchange Factors/metabolism |
| مستخلص: | Fibronectin (FN)-binding integrins control a variety of cellular responses through Rho GTPases. The FN-binding integrins, αvβ3 and α5β1, are known to induce different effects on cell morphology and motility. Here, we report that FN-bound αvβ3 integrin, but not FN-bound α5β1 integrin, triggers the dissociation of the RhoA GEF Lfc (also known as GEF-H1 and ARHGEF2 in humans) from microtubules (MTs), leading to the activation of RhoA, formation of stress fibres and maturation of focal adhesions (FAs). Conversely, loss of Lfc expression decreases RhoA activity, stress fibre formation and FA size, suggesting that Lfc is the major GEF downstream of FN-bound αvβ3 that controls RhoA activity. Mechanistically, FN-engaged αvβ3 integrin activates a kinase cascade involving MARK2 and MARK3, which in turn leads to phosphorylation of several phospho-sites on Lfc. In particular, S151 was identified as the main site involved in the regulation of Lfc localization and activity. Our findings indicate that activation of Lfc and RhoA is orchestrated in FN-adherent cells in an integrin-specific manner. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2023. Published by The Company of Biologists Ltd.) |
| فهرسة مساهمة: | Keywords: Actin dynamics; Fibronectin; GEF-H1; Integrin; Lfc; MARK2; MARK3; Rho GTPase; Signalling |
| المشرفين على المادة: | 0 (Integrin alphaV) 0 (Integrin alpha5beta1) 0 (Integrins) 0 (Guanine Nucleotide Exchange Factors) EC 3.6.5.2 (rhoA GTP-Binding Protein) 0 (ARHGEF2 protein, human) 0 (Rho Guanine Nucleotide Exchange Factors) |
| تواريخ الأحداث: | Date Created: 20230502 Date Completed: 20230503 Latest Revision: 20230524 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1242/jcs.260740 |
| PMID: | 37129180 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1477-9137 |
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| DOI: | 10.1242/jcs.260740 |