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

Leung CL, Sun D, Zheng M, Knowles DR, Liem RK - J. Cell Biol. (1999)

Bottom Line: 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.More importantly, we found that the COOH-terminal domain of mACF7 interacts with and stabilizes microtubules.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.

ABSTRACT
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 NH(2) 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 NH(2)-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.

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Expression of ACF7 mRNAs in the mouse embryo. Sagittal sections (A–C) and transverse sections (D–G) of an embryonic day 14.5 mouse embryo were hybridized with mACF7 antisense probe. Relative planes of sectioning for sections shown in D–G are illustrated on a schematic drawing of the embryo. In addition to ubiquitous expression of mACF7 mRNA throughout the embryo, high levels of expression are observed in the brain and spinal cord. In the brain, both ependymal layer (B, arrow) and mantle layer are heavily labeled. In the peripheral tissue, an intermediate to high level of ACF7 expression is observed in the dorsal root ganglia, olfactory epithelium (B, arrowhead), intrinsic muscle of the tongue, bronchial epithelium, and mesenchyme of the lung (B, arrows), skeletal muscle of the trunk (E, arrow), myocardium (F, arrow), and adrenal glands (G, arrow). Bars: 1 mm (A, B, D–G); and 0.1 mm (C).
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Figure 3: Expression of ACF7 mRNAs in the mouse embryo. Sagittal sections (A–C) and transverse sections (D–G) of an embryonic day 14.5 mouse embryo were hybridized with mACF7 antisense probe. Relative planes of sectioning for sections shown in D–G are illustrated on a schematic drawing of the embryo. In addition to ubiquitous expression of mACF7 mRNA throughout the embryo, high levels of expression are observed in the brain and spinal cord. In the brain, both ependymal layer (B, arrow) and mantle layer are heavily labeled. In the peripheral tissue, an intermediate to high level of ACF7 expression is observed in the dorsal root ganglia, olfactory epithelium (B, arrowhead), intrinsic muscle of the tongue, bronchial epithelium, and mesenchyme of the lung (B, arrows), skeletal muscle of the trunk (E, arrow), myocardium (F, arrow), and adrenal glands (G, arrow). Bars: 1 mm (A, B, D–G); and 0.1 mm (C).

Mentions: A partial human brain cDNA clone, KIAA0465 was found showing >80% sequence identity to mACF7 COOH terminus. According to the UniGene database, the gene coded for KIAA0465 is located on chromosome 1, between markers D1S2843 and D1S417. In mice, the mACF7 gene was mapped to chromosome 4, close to the marker D4mit11 (Bernier et al. 1996). Based on the chromosome synteny and the extensive sequence homology, the partial KIAA0465 cDNA should encode the human orthologue of mACF7. In addition, a short stretch of the mACF7 COOH terminus displays significant homology to a portion of the recently identified protein, GAR22 (Gas2 related on chromosome 22) (Fig. 2 B). This part of GAR22 is also closely related to the Gas2 protein (growth arrest–specific 2 protein) (Zucman-Rossi et al. 1996; Collavin et al. 1998). Because of this similarity, we designated this region of mACF7 as the GAR region. A schematic structure of mACF7 is depicted in Fig. 2 C. To study the expression pattern of mACF7, mouse embryos at embryonic day 14.5 were hybridized with a mACF7 ribonucleotide probe. As illustrated in Fig. 3, mACF7 was ubiquitously expressed in all tissues, with higher levels in the nervous system, muscle, lung, heart, and adrenal glands.


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

Leung CL, Sun D, Zheng M, Knowles DR, Liem RK - J. Cell Biol. (1999)

Expression of ACF7 mRNAs in the mouse embryo. Sagittal sections (A–C) and transverse sections (D–G) of an embryonic day 14.5 mouse embryo were hybridized with mACF7 antisense probe. Relative planes of sectioning for sections shown in D–G are illustrated on a schematic drawing of the embryo. In addition to ubiquitous expression of mACF7 mRNA throughout the embryo, high levels of expression are observed in the brain and spinal cord. In the brain, both ependymal layer (B, arrow) and mantle layer are heavily labeled. In the peripheral tissue, an intermediate to high level of ACF7 expression is observed in the dorsal root ganglia, olfactory epithelium (B, arrowhead), intrinsic muscle of the tongue, bronchial epithelium, and mesenchyme of the lung (B, arrows), skeletal muscle of the trunk (E, arrow), myocardium (F, arrow), and adrenal glands (G, arrow). Bars: 1 mm (A, B, D–G); and 0.1 mm (C).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2168091&req=5

Figure 3: Expression of ACF7 mRNAs in the mouse embryo. Sagittal sections (A–C) and transverse sections (D–G) of an embryonic day 14.5 mouse embryo were hybridized with mACF7 antisense probe. Relative planes of sectioning for sections shown in D–G are illustrated on a schematic drawing of the embryo. In addition to ubiquitous expression of mACF7 mRNA throughout the embryo, high levels of expression are observed in the brain and spinal cord. In the brain, both ependymal layer (B, arrow) and mantle layer are heavily labeled. In the peripheral tissue, an intermediate to high level of ACF7 expression is observed in the dorsal root ganglia, olfactory epithelium (B, arrowhead), intrinsic muscle of the tongue, bronchial epithelium, and mesenchyme of the lung (B, arrows), skeletal muscle of the trunk (E, arrow), myocardium (F, arrow), and adrenal glands (G, arrow). Bars: 1 mm (A, B, D–G); and 0.1 mm (C).
Mentions: A partial human brain cDNA clone, KIAA0465 was found showing >80% sequence identity to mACF7 COOH terminus. According to the UniGene database, the gene coded for KIAA0465 is located on chromosome 1, between markers D1S2843 and D1S417. In mice, the mACF7 gene was mapped to chromosome 4, close to the marker D4mit11 (Bernier et al. 1996). Based on the chromosome synteny and the extensive sequence homology, the partial KIAA0465 cDNA should encode the human orthologue of mACF7. In addition, a short stretch of the mACF7 COOH terminus displays significant homology to a portion of the recently identified protein, GAR22 (Gas2 related on chromosome 22) (Fig. 2 B). This part of GAR22 is also closely related to the Gas2 protein (growth arrest–specific 2 protein) (Zucman-Rossi et al. 1996; Collavin et al. 1998). Because of this similarity, we designated this region of mACF7 as the GAR region. A schematic structure of mACF7 is depicted in Fig. 2 C. To study the expression pattern of mACF7, mouse embryos at embryonic day 14.5 were hybridized with a mACF7 ribonucleotide probe. As illustrated in Fig. 3, mACF7 was ubiquitously expressed in all tissues, with higher levels in the nervous system, muscle, lung, heart, and adrenal glands.

Bottom Line: 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.More importantly, we found that the COOH-terminal domain of mACF7 interacts with and stabilizes microtubules.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.

ABSTRACT
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 NH(2) 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 NH(2)-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.

Show MeSH
Related in: MedlinePlus