Mutational evidence for control of cell adhesion through integrin diffusion/clustering, independent of ligand binding

Robert L. Yauch, Dan P. Felsenfeld, Stine Kathrein Kraeft, Lan Bo Chen, Michael Sheetz, Martin E. Hemler

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

Previous studies have shown that integrin α chain tails make strong positive contributions to integrin-mediated cell adhesion. We now show here that integrin α4 tail deletion markedly impairs static cell adhesion by a mechanism that does not involve altered binding of soluble vascular cell adhesion molecule 1 ligand. Instead, truncation of the α4 cytoplasmic domain caused a severe deficiency in integrin accumulation into cell surface clusters, as induced by ligand and/or antibodies. Furthermore, α4 tail deletion also significantly decreased the membrane diffusivity of α4β1, as determined by a single particle tracking technique. Notably, low doses of cytochalasin D partially restored the deficiency in cell adhesion seen upon α4 tail deletion. Together, these results suggest that α4 tail deletion exposes the β1 cytoplasmic domain, leading to cytoskeletal associations that apparently restrict integrin lateral diffusion and accumulation into clusters, thus causing reduced static cell adhesion. Our demonstration of integrin adhesive activity regulated through receptor diffusion/clustering (rather than through altered ligand binding affinity) may be highly relevant towards the understanding of inside-out signaling mechanisms for β1 integrins.

Original languageEnglish (US)
Pages (from-to)1347-1355
Number of pages9
JournalJournal of Experimental Medicine
Volume186
Issue number8
DOIs
StatePublished - Oct 20 1997
Externally publishedYes

Fingerprint

Cell Adhesion
Integrins
Cluster Analysis
Ligands
Cytochalasin D
Vascular Cell Adhesion Molecule-1
Adhesives
Membranes
Antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Mutational evidence for control of cell adhesion through integrin diffusion/clustering, independent of ligand binding. / Yauch, Robert L.; Felsenfeld, Dan P.; Kraeft, Stine Kathrein; Chen, Lan Bo; Sheetz, Michael; Hemler, Martin E.

In: Journal of Experimental Medicine, Vol. 186, No. 8, 20.10.1997, p. 1347-1355.

Research output: Contribution to journalArticle

Yauch, Robert L. ; Felsenfeld, Dan P. ; Kraeft, Stine Kathrein ; Chen, Lan Bo ; Sheetz, Michael ; Hemler, Martin E. / Mutational evidence for control of cell adhesion through integrin diffusion/clustering, independent of ligand binding. In: Journal of Experimental Medicine. 1997 ; Vol. 186, No. 8. pp. 1347-1355.
@article{5b69e5ff55f54e9e8cfb4f78805178f9,
title = "Mutational evidence for control of cell adhesion through integrin diffusion/clustering, independent of ligand binding",
abstract = "Previous studies have shown that integrin α chain tails make strong positive contributions to integrin-mediated cell adhesion. We now show here that integrin α4 tail deletion markedly impairs static cell adhesion by a mechanism that does not involve altered binding of soluble vascular cell adhesion molecule 1 ligand. Instead, truncation of the α4 cytoplasmic domain caused a severe deficiency in integrin accumulation into cell surface clusters, as induced by ligand and/or antibodies. Furthermore, α4 tail deletion also significantly decreased the membrane diffusivity of α4β1, as determined by a single particle tracking technique. Notably, low doses of cytochalasin D partially restored the deficiency in cell adhesion seen upon α4 tail deletion. Together, these results suggest that α4 tail deletion exposes the β1 cytoplasmic domain, leading to cytoskeletal associations that apparently restrict integrin lateral diffusion and accumulation into clusters, thus causing reduced static cell adhesion. Our demonstration of integrin adhesive activity regulated through receptor diffusion/clustering (rather than through altered ligand binding affinity) may be highly relevant towards the understanding of inside-out signaling mechanisms for β1 integrins.",
author = "Yauch, {Robert L.} and Felsenfeld, {Dan P.} and Kraeft, {Stine Kathrein} and Chen, {Lan Bo} and Michael Sheetz and Hemler, {Martin E.}",
year = "1997",
month = "10",
day = "20",
doi = "10.1084/jem.186.8.1347",
language = "English (US)",
volume = "186",
pages = "1347--1355",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "8",

}

TY - JOUR

T1 - Mutational evidence for control of cell adhesion through integrin diffusion/clustering, independent of ligand binding

AU - Yauch, Robert L.

AU - Felsenfeld, Dan P.

AU - Kraeft, Stine Kathrein

AU - Chen, Lan Bo

AU - Sheetz, Michael

AU - Hemler, Martin E.

PY - 1997/10/20

Y1 - 1997/10/20

N2 - Previous studies have shown that integrin α chain tails make strong positive contributions to integrin-mediated cell adhesion. We now show here that integrin α4 tail deletion markedly impairs static cell adhesion by a mechanism that does not involve altered binding of soluble vascular cell adhesion molecule 1 ligand. Instead, truncation of the α4 cytoplasmic domain caused a severe deficiency in integrin accumulation into cell surface clusters, as induced by ligand and/or antibodies. Furthermore, α4 tail deletion also significantly decreased the membrane diffusivity of α4β1, as determined by a single particle tracking technique. Notably, low doses of cytochalasin D partially restored the deficiency in cell adhesion seen upon α4 tail deletion. Together, these results suggest that α4 tail deletion exposes the β1 cytoplasmic domain, leading to cytoskeletal associations that apparently restrict integrin lateral diffusion and accumulation into clusters, thus causing reduced static cell adhesion. Our demonstration of integrin adhesive activity regulated through receptor diffusion/clustering (rather than through altered ligand binding affinity) may be highly relevant towards the understanding of inside-out signaling mechanisms for β1 integrins.

AB - Previous studies have shown that integrin α chain tails make strong positive contributions to integrin-mediated cell adhesion. We now show here that integrin α4 tail deletion markedly impairs static cell adhesion by a mechanism that does not involve altered binding of soluble vascular cell adhesion molecule 1 ligand. Instead, truncation of the α4 cytoplasmic domain caused a severe deficiency in integrin accumulation into cell surface clusters, as induced by ligand and/or antibodies. Furthermore, α4 tail deletion also significantly decreased the membrane diffusivity of α4β1, as determined by a single particle tracking technique. Notably, low doses of cytochalasin D partially restored the deficiency in cell adhesion seen upon α4 tail deletion. Together, these results suggest that α4 tail deletion exposes the β1 cytoplasmic domain, leading to cytoskeletal associations that apparently restrict integrin lateral diffusion and accumulation into clusters, thus causing reduced static cell adhesion. Our demonstration of integrin adhesive activity regulated through receptor diffusion/clustering (rather than through altered ligand binding affinity) may be highly relevant towards the understanding of inside-out signaling mechanisms for β1 integrins.

UR - http://www.scopus.com/inward/record.url?scp=0030840113&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030840113&partnerID=8YFLogxK

U2 - 10.1084/jem.186.8.1347

DO - 10.1084/jem.186.8.1347

M3 - Article

VL - 186

SP - 1347

EP - 1355

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 8

ER -