Jean Wilson

Jean Wilson, PhD, focuses on understanding how polarized cells such as epithelial cells and neurons establish and maintain the membrane domains that enable them to carry out their specialized functions. For example, epithelial cells that line the intestines must transport nutrients into the body while preventing pathogens, such as bacteria and viruses, from invading across the epithelium. This cellular balancing act is mediated in part by tight junctions between the cells. Current projects in the laboratory include studying the molecular machinery that regulates the assembly and maintenance of tight junctions between cells.

Membrane movement in epithelial cells performs at least two functions: 1) generation and maintenance of cell polarity, and 2) selective transport of molecules across cells. During development of cell polarity in the intestine, for example, sorting of newly synthesized proteins to the appropriate plasma membrane domain (either apical or basolateral) may occur by direct targeting from the trans-Golgi network or sorting in endosomes. In selective transepithelial transport, molecules bind to their receptors on one membrane domain, are internalized and delivered to endosomes where they are sorted into vesicles that carry them across the cell. All substances taken up by endocytosis must first traverse endosomes before being targeted to their ultimate destinations. Therefore, central to the sorting process for both cell polarity and transepithelial transport is the endosomal complex.

To study the structure and dynamics of endosomes, Dr. Wilson and her lab have screened for monoclonal antibodies against endosomal antigens and have obtained an antibody against a glycoprotein that is found in apical endosomes of the developing intestine in several species and is also present in an intestinal cell line. They are using this antibody to study the molecular structure and dynamics of endosomes.


Regulation Of Tight Junction Assembly And Epithelial Polarity By A Resident Protein Of Apical Endosomes. Source: Traffic (Copenhagen, Denmark)
February 27th, 2010 PMID: 20214753 Jean Wilson
The establishment of tight junctions and cell polarity is an essential process in all epithelia. Endotubin is an integral membrane protein found in apical endosomes of developing epithelia when tight junctions and epithelial polarity first arise. We found that the disruption of endotubin function in cells in culture by siRNA or overexpression of the C-terminal cytoplasmic domain of endotubin causes defects in organization and function of tight junctions. We observe defects in localization of tight junction proteins, reduced transepithelial resistance, increased lanthanum penetration between cells and reduced ability of cells to form cysts in three-dimensional culture. In addition, in cells overexpressing the C-terminal domain of endotubin, we observe a delay in re-establishing the normal distribution of endosomes after calcium switch. These results suggest that endotubin regulates trafficking of polarity proteins and tight junction components out of the endosomal compartment, thereby providing a critical link between a resident protein of apical endosomes and tight junctions.<br /><br />
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