Cytoskeleton and epithelial polarity.
The membrane surface of polarized epithelial cells can be divided in apical and basolateral domains that differ in molecular composition and function. Components of the cytoskeleton are involved in critical steps 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 selective transport of Golgi-derived carrier vesicles to the apical cell surface. Targeting of membrane proteins to the basolateral cell surface does not depend on microtubules but follows the constitutive bulk flow of membranes. Once inserted into the lipid bilayer several membrane proteins such as the kidney anion exchanger 1 (AE1) and the sodium pump 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 specialized sites of the plasma membrane but may also prevent these transporters from clustering and endocytosis, thus helping them to stay at the cell surface. In search of sequence motifs involved in binding of integral membrane proteins to components of the cytoskeleton we found that the binding interface of AE1 to protein 4.1 (an actin and spectrin cross-linking protein) consists of a cluster of five amino acid residues, namely IRRRY in AE1 and LEEDY on protein 4.1. This motif may play a more general role in cytoskeleton membrane linkages.
Drenckhahn
D
D
Institute of Anatomy, Julius-Maximilian University, Würzburg, FRG.
Jöns
T
T
Kollert-Jöns
A
A
Koob
R
R
Kraemer
D
D
Wagner
S
S
D000595:Amino Acid Sequence; D000818:Animals; D003598:Cytoskeletal Proteins / Q000737:chemistry; D003599:Cytoskeleton / Q000502:physiology*; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000502:physiology*; D008969:Molecular Sequence Data
D003598:Cytoskeletal Proteins