Laminins in Epithelial Cell Polarization: Old Questions in Search of New Answers
- 1Department of Surgery, The University of Chicago, Chicago, Illinois 60637-1470
- 2Biocenter Oulu, Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu 90220, Finland
- Correspondence: kmatlin{at}uchicago.edu
Abstract
Laminin, a basement membrane protein discovered in 1979, was shortly thereafter implicated in the polarization of epithelial cells in both mammals and a variety of lower organisms. To transduce a spatial cue to the intrinsic polarization machinery, laminin must polymerize into a dense network that forms the foundation of the basement membrane. Evidence suggests that activation of the small GTPase Rac1 by β1-integrins mobilizes laminin-binding integrins and dystroglycan to consolidate formation of the laminin network and initiate rearrangements of both the actin and microtubule cytoskeleton to help establish the apicobasal axis. A key coordinator of spatial signals from laminin is the serine–threonine kinase Par-1, which is known to affect dystroglycan availability, microtubule and actin organization, and lumen formation. The signaling protein integrin-linked kinase (ILK) may also play a role. Despite significant advances, knowledge of the mechanism by which assembled laminin produces a spatial signal remains fragmentary, and much more research into the complex functions of laminin in polarization and other cellular processes is needed.