Polarized epithelial cells line every organ and are of utmost importance for the function of the human body. Central to epithelial cell function is the establishment and maintenance of biochemically and functionally distinct membrane domains, the apical membrane facing the lumen of an organ and the basolateral membrane that is in contact with connective tissues. Both membranes are separated by tight junctions. To maintain this architecture, epithelial cells must continuously sort newly synthesized and internalized transmembrane receptors to the correct membrane domains in the biosynthetic and endocytic pathways. Our work focuses on the molecular mechanisms that ensure correct targeting to the basolateral membrane from a central sorting station, the recycling endosomes. Previously we showed that cargos destined for the basolateral membrane are recognized by the epithelial-specific clathrin adaptor complex AP-1B for incorporation into AP-1B vesicles. This grant application proposes to follow up on these findings and to investigate the molecular mechanisms of AP-1B function, membrane recruitment, and regulation of the AP-1B-dependent pathway from recycling endosomes to the basolateral membrane. We will employ genetical, biochemical, and cell biological methods to accomplish our research goals.

Public Health Relevance

The primary function of epithelial cells is to ensure the correct nutrient and waste product exchange between the body and the environment. To fulfill these different functions, the surface of epithelial cells is divided into biochemically and functionally distinct membrane domains. Our long-term goal is to understand how polarized epithelial cells establish and maintain this asymmetry with a focus on processes that lead to correct targeting of transmembrane receptors to the membrane domain that faces connective tissues and neighboring cells.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Membrane Biology and Protein Processing (MBPP)
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Ainsztein, Alexandra M
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Northwestern University at Chicago
Anatomy/Cell Biology
Schools of Medicine
United States
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Kang, Richard S; Folsch, Heike (2011) ARH cooperates with AP-1B in the exocytosis of LDLR in polarized epithelial cells. J Cell Biol 193:51-60
Shteyn, Elina; Pigati, Lucy; Folsch, Heike (2011) Arf6 regulates AP-1B-dependent sorting in polarized epithelial cells. J Cell Biol 194:873-87
Cook, Rita Nokes; Ang, Su Fen; Kang, Richard Seung-on et al. (2011) Analyzing the function of small GTPases by microinjection of plasmids into polarized epithelial cells. J Vis Exp :
Reales, Elena; Sharma, Nikunj; Low, Seng Hui et al. (2011) Basolateral sorting of syntaxin 4 is dependent on its N-terminal domain and the AP1B clathrin adaptor, and required for the epithelial cell polarity. PLoS One 6:e21181
Fields, Ian C; King, Shelby M; Shteyn, Elina et al. (2010) Phosphatidylinositol 3,4,5-trisphosphate localization in recycling endosomes is necessary for AP-1B-dependent sorting in polarized epithelial cells. Mol Biol Cell 21:95-105
Kang, Richard S; Folsch, Heike (2009) An old dog learns new tricks: novel functions of the exocyst complex in polarized epithelia in animals. F1000 Biol Rep 1:nihpa159599
Folsch, Heike; Mattila, Polly E; Weisz, Ora A (2009) Taking the scenic route: biosynthetic traffic to the plasma membrane in polarized epithelial cells. Traffic 10:972-81
Nokes, Rita L; Fields, Ian C; Collins, Ruth N et al. (2008) Rab13 regulates membrane trafficking between TGN and recycling endosomes in polarized epithelial cells. J Cell Biol 182:845-53
Folsch, Heike (2008) Regulation of membrane trafficking in polarized epithelial cells. Curr Opin Cell Biol 20:208-13
Yap, Chan Choo; Nokes, Rita L; Wisco, Dolora et al. (2008) Pathway selection to the axon depends on multiple targeting signals in NgCAM. J Cell Sci 121:1514-25

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