Selective control of basolateral membrane protein polarity by cdc42

The rho GTPase cdc42 is implicated in several aspects of cell polarity. A r ecent study (Kroschewski R, Hall A, Mellman I. Nat Cell Biol 1999;1:8-13) d emonstrated that a dominant negative mutant of cdc42 abolishes the polarity of basolateral membrane proteins in MDCK cells, but did not elucidate whet her 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 previou sly induced to overexpress mutant forms of cdc42. GTPase-deficient and domi nant negative cdc42 did not affect the apical targeting of a newly synthesi zed apical membrane protein, but reversed to apical the distribution of two exogenous basolateral membrane proteins. In striking contrast, GTPase-defi cient cdc42 did not affect polarized exocytosis of endogenous soluble prote ins, either apical or basolateral. The exquisitely selective regulation of polarized protein targeting by cdc42 may allow cells to fine-tune their mem brane composition in response to extracellular signals during development, migration and in response to injury.