Establishment and Maintenance of Cell Polarity

Epithelial cells play a pivotal role in the development of multicellular animals; their dynamic cell shape changes help orchestrate the morphogenesis of both individual organs and of the embryo as a whole. Central to this process is the establishment of epithelial cell polarity. Epithelial cells differentiate into two biochemically distinct plasma membrane domains, the apical and the basolateral domain, and it is essential for epithelial cell function that the correct proteins are targeted to each of these regions. This sorting process is faithfully recapitulated in epithelial cell lines, making them an ideal model system for analyzing how plasma membrane proteins are sorted to their respective plasma membrane domains.

My laboratory studies the mechanisms that control protein sorting in polarized epithelial cells. Specifically, we have demonstrated that the epithelial cell specific clathrin-adaptor complex AP-1B mediates the delivery of respective proteins to the basolateral membrane in clathrin-coated vesicles. A major focus of my laboratory is the identification of new proteins that interact specifically with AP-1B and help in orchestrating AP-1B vesicle formation, budding and subsequent fusion. Specifically we sought to elucidate how AP-1B facilitates the membrane recruitment of subunits of the exocyst complex, which is needed for subsequent recognition of the target site.

By better understanding the process by which epithelial cells maintain polarity, we will shed light on how epithelial cells become involved in metastatic cancer or polycystic kidney disease.

Fölsch, H., Ohno, H., Bonifacino, J.S. and Mellman, I. (1999): "A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells." Cell, 99, 189-198

Fölsch, H., Pypaert M., Peter Schu and Mellman, I. (2001): "Distribution and function of AP-1 clathrin adaptor complexes in polarized epithelial cells. " JCB., 152(3), 595-606

Ang, A., Fölsch, H., Ulla-Maija Koivisto, and Mellman, I. (2003): "The Rab8 GTPase selectively controls AP-1B-dependent basolateral transport in polarized MDCK cells." JCB, 163(2), 339-350

Fölsch, H., Pypaert, M., Maday, S., Pelletier, L., and Mellman, I. (2003): "The AP-1A and AP-1B clathrin adaptors define biochemically and functionally distinct membrane domains." JCB, 163(2), 351-362

Fölsch, H (2005): "The building blocks for basolateral vesicles in polarized epithelial cells." TRENDS in Cell Biology, 15(4), 222-228.

Fields, I.C., Pypaert, M., Shteyn, E., Proux-Gillardeaux, V., Kang, R.S., Galli, T., and Fölsch, H. (2007): "v-SNARE cellubrevin controls basolateral sorting of AP-1B-dependent cargo in polarized epithelial cells." JCB, 177, 477-488.

View all publications by publications by Heike Fölsch listed in the National Library of Medicine (PubMed).