PROMOTION OF MICROTUBULE ASSEMBLY BY OLIGOCATIONS - COOPERATIVITY BETWEEN CHARGED GROUPS

The rate and, to a lesser degree, the extent of microtubule assembly f rom rat brain tubulin is enhanced by oligocations such as polyamines, melittin, polybasic drugs, oligolysines, and oligoarginines. The effec t is cooperative for degrees of polymerization up to seven for oligoly sines and up to five for oligoarginines and is interpreted as an inter action with up to seven closely spaced anionic charges. Microtubules s o formed appear to be normal by electron microscopy, and by salt, colc hicine, and cold sensitivities. Lysyl residues in excess of seven (or five for arginine) in larger oligomers interact nearly noncooperativel y. Separation of lysyl charges by intercalation of alanyl residues red uced assembly promoting potency for hexalysines. The cooperative porti on of the response is most likely associated with the highly acidic ex treme C termini of tubulin because their removal with limited subtilis in treatment markedly reduces oligolysine potency. However, some coope rative interactions with oligocations can also occur with more widely spaced anionic charges elsewhere in tubulin. The potential role of oli gocations in the intracellular regulation of microtubule assembly is d iscussed.