Microtubule actin cross-linking factor (MACF): A hybrid of dystonin and dystrophin that can interact with the actin and microtubule cytoskeletons

We cloned and characterized a full-length cDNA of mouse actin cross-linking family 7 (mACF7) by sequential rapid amplification of cDNA ends-PCR, The c ompleted mACF7 cDNA is 17 kb and codes for a 608-kD protein. The closest re lative of mACF7 is the Drosophila protein Kakapo, which shares similar arch itecture with mACF7, mACF7 contains a putative actin-binding domain and a p lakin-like domain that are highly homologous to dystonin (BPAG1-n) at its N H2 terminus. However, unlike dystonin, mACF7 does not contain a coiled-coil rod domain; instead, the rod domain of mACF7 is made up of 23 dystrophin-l ike spectrin repeats. At its COOH terminus, mACF7 contains two putative EF- hand calcium-binding motifs and a segment homologous to the growth arrest-s pecific protein, Gas2. In this paper, we demonstrate that the NH,terminal a ctin-binding domain of mACF7 is functional both in vivo and in vitro. More importantly, we found that the COOH-terminal domain of mACF7 interacts with and stabilizes microtubules, In transfected cells full-length mACF7 can as sociate not only with actin but also with microtubules, Hence, we suggest a modified name: MACF (microtubule actin cross-linking factor), The properti es of MACF are consistent with the observation that mutations in kakapo cau se disorganization of microtubules in epidermal muscle attachment cells and some sensory neurons.