Role of Kinesin Family Members in Epithelial Polarization
Research in my lab is centered on the question of how cells generate and maintain polarity in vivo. Essential to the development of cell polarity is the targeted delivery of membrane proteins from sites of synthesis through the cytoplasm to the appropriate cell surface domain. Secretory transport is mediated by microtubule (MT)-associated mechanochemical motors kinesin(s) and dynein, which move along MT tracks. The existence of >35 human kinesin family members suggests that individual motors may specify membrane targeting of diverse cargoes and thus that they are likely involved in mediating events associated with polarization in vivo. The goal of our research is to evaluate directly the role of kinesins in specifying cellular asymmetry during epithelial polarization using intestinal epithelial cell lines as a model.In the lab we are using a combination of molecular biology and live-cell imaging approaches to assess the role of individual kinesin(s) in orchestrating protein targeting events associated with generating and maintaining polarity. We are currently attempting to (1) identify changes in the expression and/or activity of kinesin family members during epithelial polarization, (2) define the kinesin(s) responsible for trafficking of specific cargoes before and after cells polarize in culture, (3) identify proteins that interact with and modify the activity of individual kinesins and (4) elucidate how signaling cascades, initiated by polarizing and other stimuli may effect the expression and activity of kinesins in epithelial cells.