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© The Rockefeller University Press, 0021-9525/1999//1275 $5.00
The Journal of Cell Biology, Volume 147, Number 6, , 1999 1275-1286

Original Article

Microtubule Actin Cross-Linking Factor (Macf)

: A Hybrid of Dystonin and Dystrophin That Can Interact with the Actin and Microtubule Cytoskeletons



Conrad L. Leunga, Dongming Suna, Min Zhenga, David R. Knowlesa, and Ronald K.H. Liema

a Department of Pathology and Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032
Department of Pathology, Columbia University College of Physicians and Surgeons, 630 West 168th St., New York, NY 10032.(212) 305-5498(212) 305-4078

rkl2{at}columbia.edu

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 completed mACF7 cDNA is 17 kb and codes for a 608-kD protein. The closest relative of mACF7 is the Drosophila protein Kakapo, which shares similar architecture with mACF7. mACF7 contains a putative actin-binding domain and a plakin-like domain that are highly homologous to dystonin (BPAG1-n) at its NH2 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-like spectrin repeats. At its COOH terminus, mACF7 contains two putative EF-hand calcium-binding motifs and a segment homologous to the growth arrest–specific protein, Gas2. In this paper, we demonstrate that the NH2-terminal actin-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 associate not only with actin but also with microtubules. Hence, we suggest a modified name: MACF (microtubule actin cross-linking factor). The properties of MACF are consistent with the observation that mutations in kakapo cause disorganization of microtubules in epidermal muscle attachment cells and some sensory neurons.

Key Words: actin cross-linking family 7 (ACF7) • plakin • actin • microtubule • cytoskeleton

© 1999 The Rockefeller University Press

Abbreviations used in this paper: ABD, actin-binding domain; ACF7, actin cross-linking family 7; BPAG1, bullous pemphigoid antigen 1; GAR22, Gas2 related on chromosome 22; Gas2, growth arrest–specific 2 protein; IF, intermediate filament; MACF, microtubule actin cross-linking factor; mACF7, mouse ACF7; MAP, MT-associated protein; MF, microfilament; MT, microtubule; RACE, rapid amplification of cDNA ends.


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J. Cell Biol. 1999 147: 1-2. [Full Text] [PDF]





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