Microtubule Motors in Establishment of Epithelial Cell Polarity

Epithelial cells play a key role in insuring physiological homeostasis by acting as a barrier between the outside environment and internal organs. They are also responsible for the vectorial transport of ions and fluid essential to the function of many organs. To accomplish these tasks, epithelial cells must generate an asymmetrically organized plasma membrane comprised of structurally and functionally distinct apical and basolateral membranes. Adherent and occluding junctions, respectively, anchor cells within a layer and prevent lateral diffusion of proteins in the outer leaflet of the plasma membrane and restrict passage of proteins and solutes through intercellular spaces. At a fundamental level, the establishment and maintenance of epithelial polarity requires that signals initiated at cell-substratum and cell-cell adhesions are transmitted appropriately and dynamically to the cytoskeleton, to the membrane-trafficking machinery, and to the regulation of occluding and adherent junctions. Rigorous descriptive and mechanistic studies published over the last 50 years have provided great detail to our understanding of epithelial polarization. Yet still, critical early steps in morphogenesis are not yet fully appreciated. In this review, we discuss how cytoskeletal motor proteins, primarily kinesins, contribute to coordinated modification of microtubule and actin arrays, formation and remodeling of cell adhesions to targeted membrane trafficking, and to initiating the formation and expansion of an apical lumen.