Altered expression and regulation of the alpha 5beta1 integrin-fibronectin receptor lead to reduced amounts of functional alpha5beta1 heterodimer on the plasma membrane of senescent human diploid fibroblasts

Experimental Cell Research
Q HuS Goldstein

Abstract

Previously, we reported that fibronectin (FN) mRNA was overexpressed in normal late-passage (old) and pre- maturely senescent Werner syndrome (WS) fibroblasts when compared to normal early-passage (young) cells (Murano et al. Mol. Cell. Biol. 11, 3905-3914, 1991). Therefore, we investigated the expression and function of the alpha5 beta1 FN receptor (FNR), a member of the integrin family, in young and senescent normal and WS cells. Levels of the alpha5 polypeptide, a unique subunit of the alpha5 beta1 FNR, were reduced in old cells, so that old cells produced fewer alpha5 beta1 heterodimers on the plasma membrane. The reduced levels of alpha5 polypeptide might be due to deficient translation and/or nonfunctional alpha5 mRNA since increased mRNA levels and unchanged polypeptide turnover were found in these cells. Moreover, the alpha5 polypeptides on the senescent cell surface were less accessible to monoclonal antibody, suggesting sequestration of this subunit, which might affect receptor-ligand binding. In contrast, beta1 subunit, a common subunit for the beta1 integrin subfamily, showed relatively stable levels during cellular aging, but underwent slower intracellular processing. Old cells exhibited reduced attachment to FN, w...Continue Reading

Citations

Dec 6, 2003·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Hai ZhangGloria A Gronowicz
Dec 1, 2006·International Journal of Colorectal Disease·Julia BrenmoehlGerhard Rogler
Oct 31, 2003·The Journal of Biological Chemistry·Loredana MoroMargherita Greco
Jul 4, 2012·Biologie aujourd'hui·Jacqueline Labat-Robert
Nov 12, 1998·Trends in Biochemical Sciences·L VighJ L Harwood
Jun 27, 2002·Seminars in Cancer Biology·J Labat-Robert

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