FUNCTIONAL SPECIALIZATION OF STABLE AND DYNAMIC MICROTUBULES IN PROTEIN TRAFFIC IN WIF-B CELLS

We found that the magnesium salt of ilimaquinone, named 201-F, specifi cally disassembled dynamically unstable microtubules in fibroblasts an d various epithelial cell lines. Unlike classical tubulin-interacting drugs such as nocodazole or colchicine which affect all classes of mic rotubules, 201-F did not depolymerize stable microtubules. In WIF-B-po larized hepatic cells, 201-F disrupted the Golgi complex and inhibited albumin and alphal-antitrypsin secretion to the same extent as nocoda zole. By contrast, 201-F did not impair the transport of membrane prot eins to the basolateral surface, which was only affected by the total disassembly of cellular microtubules. Transcytosis of two apical membr ane proteins-the alkaline phosphodiesterase B10 and dipeptidyl peptida se IV-was affected to the same extent by 201-F and nocodazole. Taken t ogether, these results indicate that only dynamically unstable microtu bules are involved in the transport of secretory proteins to the plasm a membrane, and in the transcytosis of membrane proteins to the apical surface. By contrast, stable microtubules, which are not functionally affected by 201-F treatment, are involved in the transport of membran e proteins to the basolateral surface. By specifically disassembling h ighly dynamic microtubules, 201-F is an invaluable tool with which to study the functional specialization of stable and dynamic microtubules in living cells.