Par-1 promotes a hepatic mode of apical protein trafficking in MDCK cells

doi:10.1073/pnas.0403684101

Par-1 promotes a hepatic mode of apical protein trafficking in MDCK cells

Dyson Vision Research Institute, Weill Medical College of Cornell University, New York, NY 10021

Edited by Marilyn Gist Farquhar, University of California at San Diego, La Jolla, CA, and approved August 2, 2004 (received for review May 24, 2004)

Abstract

Simple (i.e., nonstratified) epithelial cells use two different routes to target their newly synthesized luminal plasma membrane proteins to the cell surface: a direct route from the Golgi complex, as in the kidney-derived MDCK cell line, or an indirect route that involves a intermediate stop at the ab-luminal (basolateral) membrane, as in hepatocytes. The mechanisms or proteins responsible for these different protein targeting strategies are not known. Here, we show that increased expression of EMK1, a mammalian ortholog of Caenorhabditis elegans Par-1, in MDCK cells promotes a switch from a direct to a transcytotic mode of apical protein delivery and other trafficking changes typical of hepatocytes. These results, together with our recent demonstration that PAR-1 promotes morphological features of hepatocytes in MDCK cells, indicate that Par-1 modulates the developmental decision to build a columnar versus a hepatic epithelial cell. To our knowledge, Par-1 is the first gene assigned to this task in epithelial morphogenesis.

Footnotes

↵ * To whom correspondence should be addressed at: Dyson Vision Research Institute, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021. E-mail: amuesch{at}mail.med.cornell.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: MT, microtubule; GPI, glycosylphosphatidylinositol; TGN, trans-Golgi network; DPPIV, dipeptidyl peptidase IV; solDPPIV, soluble form of rat DPPIV; LDLR, low-density lipoprotein receptor; VAC, vacuolar apical compartment; Tf, transferrin; dIgA, dimeric IgA.