Investigating the roles of cytoplasmic proteins talin and kindlin3 in integrin LFA-1 activation

149 p.

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Bibliographic Details
Main Author:	Li, Yan Feng
Other Authors:	Tan Suet Mien
Format:	Theses and Dissertations
Published:	2011
Subjects:	DRNTU::Science::Biological sciences::Cytology
Online Access:	https://hdl.handle.net/10356/47455
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Institution:	Nanyang Technological University

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spelling	sg-ntu-dr.10356-474552023-02-28T18:36:54Z Investigating the roles of cytoplasmic proteins talin and kindlin3 in integrin LFA-1 activation Li, Yan Feng Tan Suet Mien School of Biological Sciences DRNTU::Science::Biological sciences::Cytology 149 p. The integrin aL(32 (LFA-1, CD 11 a/CD 18) mediates leukocyte adhesion and migration that are required for a functional immune system. It is known that inside-out signaling triggers aL(32 conformational changes, which affect its ligand-binding affinity. At least three aL(32 affinity states (low, intermediate, and high) were described. Talin is a four-point-one ezrin radixin moesin (FERM)-domain containing cytoplasmic protein that connects aL(32 to the actin filament. The talin head domain is also known to activate aLP2 ligand binding. However, it remains to be determined whether talin promotes an intermediate or high affinity aL\|32. In the first part of this study using transfectants and T cells, we showed that talin induced an intermediate affinity aL(32 that adhered constitutively to its ligand intercellular adhesion molecule (ICAM)-l but not ICAM-3. Adhesion to ICAM-3 was induced when an additional exogenous activating agent was included. Similar profiles were observed with soluble ICAMs. In addition, the intermediate affinity aL(32 induced by talin allowed adhesion and migration of T cells on immobilized ICAMs. Kindlins are also FERM-domain containing proteins that have been reported to regulate integrin function. In the second part of this study, we showed that kindlin3 co-activates aLp2 together with talin, and that its pleckstrin homology (PH) domain and F3 subdomain are required in the process. Interestingly, kindlin3-overexpressed T cells showed reduced migration on ICAM-1. Immunofluorescence staining suggest that kindlin3 and talin both localize at the leading edge of migratory T cells. It remains to be determined how kindlin3 reduces the migration of T cells. It would also be interesting to investigate at the molecular level the cooperativity of kindlin3 and talin in the regulation of CLL$2 function. DOCTOR OF PHILOSOPHY (SBS) 2011-12-27T08:18:56Z 2011-12-27T08:18:56Z 2009 2009 Thesis Li, Y. F. (2009). Investigating the roles of cytoplasmic proteins talin and kindlin3 in integrin LFA-1 activation. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/47455 10.32657/10356/47455 Nanyang Technological University application/pdf
institution	Nanyang Technological University
building	NTU Library
continent	Asia
country	Singapore Singapore
content_provider	NTU Library
collection	DR-NTU
topic	DRNTU::Science::Biological sciences::Cytology
spellingShingle	DRNTU::Science::Biological sciences::Cytology Li, Yan Feng Investigating the roles of cytoplasmic proteins talin and kindlin3 in integrin LFA-1 activation
description	149 p.
author2	Tan Suet Mien
author_facet	Tan Suet Mien Li, Yan Feng
format	Theses and Dissertations
author	Li, Yan Feng
author_sort	Li, Yan Feng
title	Investigating the roles of cytoplasmic proteins talin and kindlin3 in integrin LFA-1 activation
title_short	Investigating the roles of cytoplasmic proteins talin and kindlin3 in integrin LFA-1 activation
title_full	Investigating the roles of cytoplasmic proteins talin and kindlin3 in integrin LFA-1 activation
title_fullStr	Investigating the roles of cytoplasmic proteins talin and kindlin3 in integrin LFA-1 activation
title_full_unstemmed	Investigating the roles of cytoplasmic proteins talin and kindlin3 in integrin LFA-1 activation
title_sort	investigating the roles of cytoplasmic proteins talin and kindlin3 in integrin lfa-1 activation
publishDate	2011
url	https://hdl.handle.net/10356/47455
_version_	1759854531773988864

Investigating the roles of cytoplasmic proteins talin and kindlin3 in integrin LFA-1 activation

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