IDENTIFICATION OF A NOVEL MICROTUBULE-BINDING DOMAIN IN MICROTUBULE-ASSOCIATED PROTEIN-1A (MAP1A)

Several microtubule-associated proteins (MAPs) have been shown to bind to microtubules via short sequences with repeated amino acids motifs. A microtubule-binding domain has hitherto not been defined for the ad ult brain microtubule-associated protein 1A (MAP1A). We have searched for a microtubule-binding domain by expressing different protein regio ns of MAP1A in cultured cell lines using cDNA constructs. One construc t included an area with homology to the microtubule-binding domain of MAP1B (Noble et al. (1989) J. Cell Biol. 109, 437-448), but this did n ot bind to microtubules in transfected cells. Further investigation of other areas of MAP1A revealed a protein domain, capable of autonomous ly binding to microtubules, which bears no homology to any previously described microtubule-binding sequence. This MAP1A domain is rich in c harged amino acids, as are other mammalian microtubule-binding domains , but unlike them has no identifiable sequence repeats. Whereas all pr eviously described mammalian microtubule-binding domains are basic, th is novel microtubule-binding domain of MAP1A is acidic. The expression of this polypeptide in cultured cell lines led to a rearrangement of the microtubules in a pattern distinct from that produced by MAP2 or t au, and increased their resistance to treatment with the microtubule d epolymerising agent nocodazole. When the MAP1A microtubule-binding dom ain was co-expressed in cultured cell lines together with MAP2c, the M AP1A microtubule-binding domain was able to bind to the MAP2c-induced microtubule bundles. These results suggest that different microtubule- binding sequences have a common ability to stabilise microtubules but differ in their influence on microtubule arrangement in the cell. This may be significant in neurons, where microtubule-associated proteins with different microtubule-binding sequences are expressed in differen t cell compartments and at different times during development.