Lewandowski KT, Piwnica-Worms H

The establishment and maintenance of cell polarity is an essential property governing organismal homeostasis, and loss of polarity is a common feature of cancer cells. The ability of epithelial cells to establish apical-basal polarity depends on intracellular signals generated from polarity proteins such as Par-1 as well as extracellular signals ...

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generated through cell contacts with the extracellular matrix (ECM). Par-1 has a well-established role in regulating cell-cell contacts in the form of tight junctions by phosphorylating Par-3. In addition, Par-1 has been shown to impact cell-ECM interactions by regulating laminin receptor localization and laminin deposition on the basal surface of epithelial cells. Laminins are major structural and signaling components of basement membranes (BM), a sheet of specialized ECM underlying epithelia. In this study we identify RNF41, an E3 ubiquitin ligase, as a novel Par-1 effector in the cell-ECM pathway. Par-1 binds to and phosphorylates RNF41 on serine 254. Phosphorylation of RNF41 by Par-1 is required for epithelial cells to localize laminin-111 receptors to their basolateral surfaces and to properly anchor to laminin-111. In addition, phosphorylation of RNF41 is required for epithelial cells to establish apical-basal polarity. Our data suggests that phosphorylation of RNF41 by Par-1 regulates basolateral membrane targeting of laminin-111 receptors, thereby facilitating cell anchorage to laminin-111 and ultimately forming the cell-ECM contacts required for epithelial cells to establish apical-basal cell polarity.

Date: Nov. 20, 2013

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