Professor, BIO5 Institute
Professor, Cancer Biology - GIDP
Professor, Neuroscience - GIDP
Director, Willed Body Program
All eukaryotic cells are divided into membrane-bound compartments termed organelles. Organelles allow cells to segregate enzymatic reactions that are necessary for metabolism and growth. A central issue in cell biology is how cells generate and maintain the different compositions of organelles. Work in my laboratory focuses on organelles (called endosomes) that are involved in both sorting of newly synthesized proteins and uptake of substances from outside the cell.
An archetypical example of membrane sorting occurs in epithelial cells. Epithelial tissues, like those lining the intestine and lungs, face the "outside world", forming a barrier between the inside of an organism and the environment. They can be compared to security gates, allowing substances with the correct "address" to pass through but barring entry to other molecules and organisms. The function of these cellular linings is to allow entry of some materials while preventing passage of toxins or pathogens. Epithelial cells are "polarized" i.e. they have different proteins and lipids in the membranes that face the external environment (also called the apical domain), and the internal environment (basolateral domain). In all polarized epithelial cells, asymmetry develops and is maintained by the movement of cellular membranes.
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, for example, the intestine, 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, we 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. We are using this antibody to study the molecular structure and dynamics of endosomes.
Hernandez-Deviez DJ. Wilson JM. Functional assay of ARNO and ARF6 in neurite elongation and branching. Methods in Enzymology. 404:242-52, 2005.
Gokay, K.E., R.S. Young, and J.M. Wilson. Cytoplasmic signals mediate apical early endosomal targeting of endotubin in MDCK cells. Traffic, 2:487-500, 2001.
Gokay, K.E. and Wilson, J.M. Targeting of an intestinal apical endosomal protein to apical endosomes in MDCK cells requires two sorting motifs. Traffic, 1:354-365, 2001.
-Jennifer Magdaleno, Mountain View High School, 1997
-Sophia Rangwala, Catalina Foothills High School, 2002