Sci. STKE, 19 November 2002
Integrins Uncleaved and Matrix-Free
The α subunit of most integrin α/β heterodimers undergoes an endoproteolytic cleavage, yielding a heavy and a light chain, which are linked by a disulfide bond. However, uncleaved α subunits are also present in some functional, extracellular matrix-binding integrins, although their physiological significance has not been clear. Walker et al. show that the cleavage state of the α6 integrin is regulated during chicken embryogenesis. Both cleaved and uncleaved forms of α6 are expressed at the surface of embryonic lens cells, but a switch to the uncleaved form occurs during differentiation. The uncleaved form is underglycosylated and becomes localized to the lateral cell interface of differentiating lens cells. Uncleaved integrins associated with Shc and Grb2, two molecules known to mediate integrin-initiated signaling and cell survival. The cell-cell interface is devoid of matrix proteins, suggesting ligand-independent signaling by the uncleaved integrin subunit at the time of differentiation. Underglycosylated integrins are thought to localize to lipid microdomains that are enriched in signaling molecules. The authors propose that uncleaved integrins may provide a cell survival signal during lens cell differentiation, a period when the lens becomes progressively transparent through caspase-mediated degradation of nuclei and organelles in an apoptosis-like process.
J. L. Walker, L. Zhang, A. S. Menko, A signaling role for the uncleaved form of α6 integrin in differentiating lens fiber cells. Dev. Biol. 251, 195-202 (2002). [Online Journal]
Citation: Uncleaved and Matrix-Free. Sci. STKE 2002, tw427 (2002).
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