THE TRANSITION OF MICROGLIA TO A RAMIFIED PHENOTYPE IS ASSOCIATED WITH THE FORMATION OF STABLE ACETYLATED AND DETYROSINATED MICROTUBULES

In situ and in vitro, microglia can have different morphologies, which are thought to reflect distinct physiological activities. Two extreme forms are ameboid and ramified microglia. To study cytoskeletal chang es during differentiation, we used defined cell culture systems to yie ld cultures of ameboid or ramified microglia from mouse brain, With re spect to proliferation, secretion, receptor-expression, and phagocytos is, ramified microglia was generally less active. We found that the tr ansition to a ramified phenotype was accompanied by an increase in the relative amount of acetylated and detyrosinated tubulin. Whereas the modified microtubules were restricted to regions close to the microtub ule-organizing centers (MTOCs) in ameboid cells, acetylated microtubul es were abundant in ramified cells, where they appeared to traverse fr om one process to another with no apparent anchoring at MTOCs. The inc rease in acetylated and detyrosinated microtubules was paralleled by a n increased stability against nocodazole-induced microtubule disassemb ly and by a lower rate of change in the length of the processes. Stain ing of retinal wholemounts confirmed the presence of acetylated microt ubules in ramified microglia in situ. We conclude that during the tran sition of microglia to a ramified phenotype regulated processes exist, which cause a reorganization of microtubules and a change in composit ion of the microtubule skeleton resulting in a less dynamic and more s table microtubule network. Intracellular factors that are specifically involved in microtubule stabilization in ramified microglia need to b e identified in future research and may provide a useful criterion for defining ramified microglia. (C) 1996 Wiley-Liss, Inc.