Journal of Cell Science, Vol 106, Issue 4 1131-1138, Copyright © 1993 by Company of Biologists

JOURNAL ARTICLES

Functional down-regulation of alpha 5 beta 1 integrin in keratinocytes is reversible but commitment to terminal differentiation is not

NA Hotchin, NL Kovach and FM Watt
Keratinocyte Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London, UK.

Extracellular matrix receptors of the integrin family have a dual role in the epidermis, regulating both adhesion and differentiation. Loss of contact with the extracellular matrix causes keratinocytes to become committed to terminal differentiation, and results in a decrease in the ability of the alpha 5 beta 1 integrin to bind fibronectin. We have investigated whether the decrease in ligand-binding ability is reversible and, if so, whether commitment to terminal differentiation can also be reversed. Keratinocytes that had been placed in suspension for 5 hours to induce commitment were compared with the starting population (0 hour cells) in the presence or absence of 8A2, an activating anti-beta 1 antibody. 8A2 IgG or FAb fragments increased the amount of alpha 5 beta 1 in cell extracts that bound to fibronectin-Sepharose and in the presence of 8A2 the amount of bound alpha 5 beta 1 in 0 hour and 5 hour extracts was equal. 8A2 also restored alpha 5 beta 1 function in adhesion assays of intact 5 hour cells. Ca2+, Mg2+ and Mn2+ alone, at concentrations of up to 1 mM, did not increase the adhesiveness of 5 hour cells relative to 0 hour cells; however, the effect of 8A2 on keratinocytes was dependent on Ca2+. Although 8A2 restored alpha 5 beta 1 ligand-binding ability it did not prevent committed cells from withdrawing from the cell cycle and expressing involucrin, a differentiation marker.(ABSTRACT TRUNCATED AT 250 WORDS)
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				N. Akhtar and N. A. Hotchin RAC1 Regulates Adherens Junctions through Endocytosis of E-Cadherin Mol. Biol. Cell, April 1, 2001; 12(4): 847 - 862. [Abstract] [Full Text]

				L. Levy, S. Broad, D. Diekmann, R. D. Evans, and F. M. Watt beta 1 Integrins Regulate Keratinocyte Adhesion and Differentiation by Distinct Mechanisms Mol. Biol. Cell, February 1, 2000; 11(2): 453 - 466. [Abstract] [Full Text]

				B. Harvat, A Wang, P Seth, and A. Jetten Up-regulation of p27Kip1, p21WAF1/Cip1 and p16Ink4a is associated with, but not sufficient for, induction of squamous differentiation J. Cell Sci., January 5, 1998; 111(9): 1185 - 1196. [Abstract] [PDF]

				A. Zhu and F. Watt Expression of a dominant negative cadherin mutant inhibits proliferation and stimulates terminal differentiation of human epidermal keratinocytes J. Cell Sci., January 12, 1996; 109(13): 3013 - 3023. [Abstract] [PDF]

				D. Hudson, J Sleeman, and F. Watt CD44 is the major peanut lectin-binding glycoprotein of human epidermal keratinocytes and plays a role in intercellular adhesion J. Cell Sci., January 5, 1995; 108(5): 1959 - 1970. [Abstract] [PDF]