Received July 20, 2007
Accepted on October 4, 2007

BASIC RESEARCH

Human Podocytes Adhere to the KRGDS Motif of the 345 Collagen IV Network

Corina M. Borza ^*, Dorin-Bogdan Borza ^*, Vadim Pedchenko ^*, Moin A. Saleem , Peter W. Mathieson , Yoshikazu Sado , Heather M. Hudson ¹, Ambra Pozzi ^*||¶, Juan Saus ^**, Dale R. Abrahamson , Roy Zent ^*||¶, and Billy G. Hudson ^*1

*Division of Nephrology, ||Department of Cancer Biology, Department of Cell and Developmental Biology, Vanderbilt Medical Center, Nashville, Tennessee; ¶Veterans Affairs Medical Center, Nashville, Tennessee; Academic and Children’s Renal Unit, University of Bristol, Southmead Hospital, Bristol, United Kingdom; Shigei Medical Research Institute, Okayama, Japan; Department of Molecular and Integrative Physiology, Kansas Medical Center, Kansas City, Missouri; **Centro de Investigación Príncipe Felipe and Departamento de Bioquímica y Biología Molecular, Universitat de Valencia, Valencia, Spain; and Department of Cell Biology, Kansas Medical Center, Kansas City, Missouri

¹ To whom correspondence should be addressed. E-mail: billy.hudson{at}vanderbilt.edu.

	Abstract

Podocyte adhesion to the glomerular basement membrane is required for proper function of the glomerular filtration barrier. However, the mechanism whereby podocytes adhere to collagen IV networks, a major component of the glomerular basement membrane, is poorly understood. The predominant collagen IV network is composed of triple helical protomers containing the 345 chains. The protomers connect via the trimeric noncollagenous (NC1) domains to form hexamers at the interface. Because the NC1 domains of this network can potentially support integrin-dependent cell adhesion, it was determined whether individual NC1 monomers or 345 hexamers support podocyte adhesion. It was found that, although human podocytes did not adhere to NC1 domains proper, they did adhere via integrin v3 to a KRGDS motif located adjacent to 3NC1 domains. Because the KRGDS motif is a site of phosphorylation, its interactions with integrin v3 may play a critical role in cell signaling in physiologic and pathologic states.