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

Microtubule actin cross-linking factor (MACF): a hybrid of dystonin and dystrophin that can interact with the actin and microtubule cytoskeletons.
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DOI:
10.1083/jcb.147.6.1275
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发表时间:
1999-12-13
影响因子:
7.8
通讯作者:
Liem, R K
Liem, R K
中科院分区:
生物学1区
文献类型:
--
作者:
Leung, C L;Sun, D;Zheng, M;Knowles, D R;Liem, R K

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我们克隆了小鼠肌动蛋白交联家族7 (mACF7)的全长cDNA,并利用cDNA末端序列快速扩增技术对其进行了鉴定。完整的mACF7 cDNA全长17kb,编码608-kD蛋白。mACF7最近的亲戚是果蝇蛋白Kakapo,它与mACF7有相似的结构。mACF7在其NH2末端含有一个假定的肌动蛋白结合结构域和一个与dystonin (BPAG1-n)高度同源的plakin样结构域。然而,与dystonin不同的是,mACF7不包含线圈状棒结构域;相反,mACF7的杆状结构域由23个类似肌营养不良蛋白的谱蛋白重复序列组成。在其COOH末端,mACF7含有两个假定的EF-hand钙结合基体和一个与生长抑制特异性蛋白Gas2同源的片段。在本文中,我们证明了mACF7的nh2末端肌动蛋白结合域在体内和体外都具有功能。更重要的是,我们发现mACF7的cooh末端结构域与微管相互作用并稳定微管。在转染的细胞中,全长mACF7不仅可以与肌动蛋白结合,还可以与微管结合。因此,我们建议将其命名为MACF(微管肌动蛋白交联因子)。MACF的特性与鸮鹦鹉突变导致表皮肌肉附着细胞和部分感觉神经元微管紊乱的观察结果一致。
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.