Selective control of basolateral membrane protein polarity by cdc42.
The rho GTPase cdc42 is implicated in several aspects of cell polarity. A recent study (Kroschewski R, Hall A, Mellman I. Nat Cell Biol 1999;1:8-13) demonstrated that a dominant negative mutant of cdc42 abolishes the polarity of basolateral membrane proteins in MDCK cells, but did not elucidate whether this effect was selective for basolateral proteins or nonselective for all secreted proteins. To answer this question, we analyzed the polarity of newly synthesized membrane and soluble proteins in MDCK cell lines previously induced to overexpress mutant forms of cdc42. GTPase-deficient and dominant negative cdc42 did not affect the apical targeting of a newly synthesized apical membrane protein, but reversed to apical the distribution of two exogenous basolateral membrane proteins. In striking contrast, GTPase-deficient cdc42 did not affect polarized exocytosis of endogenous soluble proteins, either apical or basolateral. The exquisitely selective regulation of polarized protein targeting by cdc42 may allow cells to fine-tune their membrane composition in response to extracellular signals during development, migration and in response to injury.
Cohen
D
D
Dyson Institute of Vision Research, Department of Biochemistry, Joan and Sanford Weill Medical College of Cornell University, New York, New York, 10021, USA.
Müsch
A
A
Rodriguez-Boulan
E
E
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D027682:Cation Transport Proteins; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement; D004285:Dogs; D019084:Fluorescent Antibody Technique, Indirect; D020558:GTP Phosphohydrolases / Q000378:metabolism; D005799:Genes, Dominant; D006801:Humans; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D013752:Tetracycline / Q000494:pharmacology; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
D027682:Cation Transport Proteins; D011500:Protein Synthesis Inhibitors; D000251:Adenosine Triphosphatases; D020558:GTP Phosphohydrolases; C021838:sodium-translocating ATPase; D020764:cdc42 GTP-Binding Protein; D013752:Tetracycline