Par1b Promotes Hepatic-type Lumen Polarity in Madin Darby Canine Kidney Cells via Myosin II- and E-Cadherin–dependent Signaling

Abstract

Kidney-derived Madin Darby canine kidney (MDCK) cells form lumina at their apices, and target luminal proteins to an intracellular vacuolar apical compartment (VAC) when prevented from polarizing. Hepatocytes, by contrast, organize their luminal surfaces (the bile canaliculi; BC) between their lateral membranes, and, when nonpolarized, they display an intracellular luminal compartment that is distinct from the VACs of MDCK cells. Overexpression of the serine/threonine kinase Par1b/EMK1/MARK2 induces BC-like lateral lumina and a hepatic-type intracellular luminal compartment in MDCK cells, suggesting a role for Par1b in the branching decision between kidney- and hepatic-type epithelial phenotypes. Here, we report that Par1b promotes lateral lumen polarity in MDCK cells independently of Ca(2+)-mediated cell-cell adhesion by inhibiting myosin II in a rho kinase-dependent manner. Polarization was inhibited by E-cadherin depletion but promoted by an adhesion-defective E-cadherin mutant. By contrast, apical surface formation in control MDCK cells required Ca(2+)-dependent cell-cell adhesion, but it occurred in the absence of E-cadherin. We propose that E-cadherin, when in an adhesion-incompetent state at the lateral domain, serves as targeting patch for the establishment of lateral luminal surfaces. E-cadherin depletion also reverted the hepatic-type intracellular luminal compartment in Par1b-MDCK cells to VACs characteristic of control MDCK cells, indicating a novel link between E-cadherin and luminal protein targeting.

Accurate Balance of the Polarity Kinase MARK2/Par-1 Is Required for Proper Cortical Neuronal Migration

“…These results may also stem from a possible effect of MARK2 on cell adhesion. Previous experiments in MDCK cells suggest that MARK2 directly affects cadherins, which impact cell adhesive properties (Elbert et al, 2006;Cohen et al, 2007). Cdk5 directly interacts with N-cadherin, and this interaction may play an important role in the abnormal neuronal migration phenotype observed in the Cdk5Ϫ/Ϫ or p35Ϫ/Ϫ mice (Kwon et al, 2000).…”

Active Rab11 and functional recycling endosome are required for E-cadherin trafficking and lumen formation during epithelial morphogenesis

“…Thus, one important consequence of sorting in the RE is the exclusive targeting of E-cadherin to the basolateral membrane to engage epithelial polarity from early stages and to ensure morphogenesis is on track thereafter. Recent studies suggest an essential role for E-cadherin early on in establishing cell polarity (7,30), and one that can be independent of cell-cell adhesion (9). Cells in these situations often retained cell-cell contacts.…”

LKB1; linking cell structure and tumor suppression

“…The MARKs promote epithelial polarization through regulation of tubulin dynamics (Hatakeyama, 2008). This is mediated through phosphorylation of microtubule-associated proteins, including tau, and involves alteration in cell contacts and in E-cadherin localization (Drewes et al, 1997;Cohen et al, 2004Cohen et al, , 2007Elbert et al, 2006). Notably, germ line deletion of MARK2 in the mouse uncovered a role in energy metabolism as MARK-deficient animals are growth retarded, have decreased adiposity and are hyperphagic (Hurov and Piwnica-Worms, 2007;.…”