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J. Biol. Chem., Vol. 279, Issue 51, 53762-53769, December 17, 2004

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Regulation of Human -Cell Adhesion, Motility, and Insulin Secretion by Collagen IV and Its Receptor ₁₁^*

Thomas Kaido, Mayra Yebra, Vincenzo Cirulli, and Anthony M. Montgomery

From the Department of Pediatrics, Islet Research Laboratory at The Whittier Institute for Diabetes, University of California at San Diego, La Jolla, California 92037

Collagens have been shown to influence the survival and function of cultured -cells; however, the utilization and function of individual collagen receptors in -cells is largely unknown. The integrin superfamily contains up to five collagen receptors, but we have determined that ₁₁ is the primary receptor utilized by both fetal and adult -cells. Cultured -cells adhered to and migrated on collagen type IV (Col-IV), and these responses were mediated almost exclusively by ₁₁. The migration of cultured -cells to Col-IV significantly exceeded that to other matrix components suggesting that this substrate is of unique importance for -cell motility. The interaction of ₁₁ with Col-IV also resulted in significant insulin secretion at basal glucose concentrations. A subset of -cells in developing islets was confirmed to express ₁₁, and this expression co-localized with Col-IV in the basal membranes of juxtaposed endothelial cells. Our findings indicate that ₁₁ and Col-IV contribute to -cell functions known to be important for islet morphogenesis and glucose homeostasis.

Received for publication, September 30, 2004

^* This work was supported by Juvenile Diabetes Research Foundation Grant JDRFI 1-20001-793 (to A. M. M) and by the Larry L. Hillblom Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Pediatrics, Islet Research Laboratory at The Whittier Institute for Diabetes, University of California at San Diego, 9894 Genesee Ave., La Jolla, CA 92037. Tel.: 858-550-2909; Fax: 858-558-3495; E-mail: ammontgo{at}ucsd.edu.

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