Skip to main content

Studies on the morphology and spreading of human endothelial cells define key inter- and intramolecular interactions for talin1.

Kopp, Petra M, Bate, Neil, Hansen, Tania M, Brindle, Nicholas P J, Praekelt, Uta, Debrand, Emmanuel, Coleman, Stacey, Mazzeo, Daniela, Goult, Benjamin T, Gingras, Alexandre R, and others. (2010) Studies on the morphology and spreading of human endothelial cells define key inter- and intramolecular interactions for talin1. European journal of cell biology, 89 (9). pp. 661-73. ISSN 1618-1298. (doi:10.1016/j.ejcb.2010.05.003) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1016/j.ejcb.2010.05.003

Abstract

Talin binds to and activates integrins and is thought to couple them to cytoskeletal actin. However, functional studies on talin have been restricted by the fact that most cells express two talin isoforms. Here we show that human umbilical vein endothelial cells (HUVEC) express only talin1, and that talin1 knockdown inhibited focal adhesion (FA) assembly preventing the cells from maintaining a spread morphology, a phenotype that was rescued by GFP-mouse talin1. Thus HUVEC offer an ideal model system in which to conduct talin structure/function studies. Talin contains an N-terminal FERM domain (comprised of F1, F2 and F3 domains) and a C-terminal flexible rod. The F3 FERM domain binds beta-integrin tails, and mutations in F3 that inhibited integrin binding (W359A) or activation (L325R) severely compromised the ability of GFP-talin1 to rescue the talin1 knockdown phenotype despite the presence of a second integrin-binding site in the talin rod. The talin rod contains several actin-binding sites (ABS), and mutations in the C-terminal ABS that reduced actin-binding impaired talin1 function, whereas those that increased binding resulted in more stable FAs. The results show that both the N-terminal integrin and C-terminal actin-binding functions of talin are essential to cell spreading and FA assembly. Finally, mutations that relieve talin auto-inhibition resulted in the rapid and excessive production of FA, highlighting the importance of talin regulation within the cell.

Item Type: Article
DOI/Identification number: 10.1016/j.ejcb.2010.05.003
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Ben Goult
Date Deposited: 07 Aug 2014 15:51 UTC
Last Modified: 13 Aug 2019 03:05 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/42124 (The current URI for this page, for reference purposes)
Goult, Benjamin T: https://orcid.org/0000-0002-3438-2807
  • Depositors only (login required):