CAVEOLIN CYCLES BETWEEN PLASMA-MEMBRANE CAVEOLAE AND THE GOLGI-COMPLEX BY MICROTUBULE-DEPENDENT AND MICROTUBULE-INDEPENDENT STEPS

Caveolin is a protein associated with the characteristic coats that de corate the cytoplasmic face of plasma membrane caveolae. Recently it w as found that exposure of human fibroblasts to cholesterol oxidase (GO ) rapidly induces caveolin to redistribute to the ER and then to the G olgi complex? and that subsequent removal of CO allows caveolin to ret urn to the plasma membrane (Smart, E. J., Y. -S. Ying, P. A. Conrad, R . G. W. Anderson. J. Cell Biol. 1994, 127:1185-1197). We now present e vidence that caveolin normally undergoes microtubule-dependent cycling between the plasma membrane and the Golgi. In cells that were treated briefly with nocodazole and then with a mixture of nocodazole plus CO , caveolin relocated from the plasma membrane to the ER and then to th e ER/Golgi intermediate compartment (ERGIC), but subsequent movement t o the Golgi was not observed. Even in the absence of CO, nocodazole ca used caveolin to accumulate in the ERGIC. Nocodazole did not retard th e movement of caveolin from the Golgi to the plasma membrane after rem oval of CO. Incubation of cells at 15 degrees followed by elevation of the temperature to 37 degrees caused caveolin to accumulate first in the ERGIC and then in the Golgi, before finally reestablishing its nor mal steady stale distribution predominantly in plasma membrane caveola e. In cells released from a 15 degrees block, movement of caveolin fro m the Golgi to the plasma membrane was not inhibited by nocodazole. Ta ken together, these results imply that caveolin cycles constitutively between the plasma membrane and the Golgi by a multi-step process, one of which, ERGIC-to-Golgi transport, requires microtubules. This novel , bidirectional pathway may indicate roles for microtubules in the mai ntenance of caveolae, and for caveolin in shuttling fatty acids and ch olesterol between the plasma membrane and the ER/Golgi system.