CYTOSKELETON AND EPITHELIAL POLARITY

The membrane surface of polarized epithelial cells can be divided in a pical and basolateral domains that differ in molecular composition and function. Components of the cytoskeleton are involved in critical ste ps of both generation and maintenance of cell polarity. Generation of polarity is controlled by microtubules that serve as uniformly aligned and polarized cytoplasmic guiding structures for the vectorial and se lective transport of Golgi-derived carrier vesicles to the apical cell surface. Targeting of membrane proteins to the basolateral cell surfa ce does not depend on microtubules but follows the constitutive bulk f low of membranes. Once inserted into the lipid bilayer several membran e proteins such as the kidney anion exchanger 1 (AE1) and the sodium p ump become immobilized at specialized microdomains of the lateral cell surface. Evidence is provided that both membrane proteins are linked via ankyrin to the spectrin-based membrane cytoskeleton that underlies the basolateral membrane domain. Linkage of these and other integral membrane proteins to the cytoskeleton may not only place them to speci alized sites of the plasma membrane but may also prevent these transpo rters from clustering and endocytosis, thus helping them to stay at th e cell surface. In search of sequence motifs involved in binding of in tegral membrane proteins to components of the cytoskeleton we found th at the binding interface of AE1 to protein 4.1 (an actin and spectrin cross-linking protein) consists of a cluster of five amino acid residu es, namely IRRRY in AE1 and LEEDY on protein 4.1. This motif may play a more general role in cytoskeleton membrane linkages.