Zasp/Cypher internal ZM-motif containing fragments are sufficient to co-localize with α-actinin -: Analysis of patient mutations
Zasp/Cypher internal ZM-motif containing fragments are sufficient to co-localize with α-actinin -: Analysis of patient mutations
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DOI：
10.1016/j.yexcr.2005.12.036
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发表时间：
2006-05-01
影响因子：
3.7
通讯作者：
Ylänne, J
中科院分区：
文献类型：
--
作者：
Klaavuniemi, T;Ylänne, J
Z带选择性剪接PDZ蛋白(ZASP/Cypher)在维持横纹肌和心肌Z盘的稳定性中起着重要作用。ZASP/Cypher通过其PDZ结构域与主要的Z-Disc肌动蛋白交联剂α-肌动蛋白相互作用。ZASP/Cypher也有一个被称为ZM-基序的保守序列，它存在于两个可选择性剪接的外显子4和6中。我们先前已经证明，包含两个相关蛋白ALP和CLP36的内部区域的ZM-基序与α-肌动蛋白杆状区相互作用，并且ZM-基序在将ALP靶向细胞中含有α-肌动蛋白的结构中起重要作用。在这里，我们发现含有ZM外显子4或6的ZASP/Cypher内部片段与α-肌动蛋白在培养的成肌细胞和非肌肉细胞中共定位。ZM共识周围130个残基的片段足以进行定位，这与我们之前对ALP的结果相似。此外，ZASP/Cypher蛋白直接与ET-肌动蛋白结合，并与碱性磷酸酶竞争结合。在抑制应力纤维组装的过程中，ZASP/Cypher和α-Actinin的共定位可能受到部分干扰，这表明ZASP/Cypher主要是在a-Actinin定位于应力纤维时与α-Actinin结合的。在心肌病患者中发现的许多点突变位于ZASP/Cypher的内部区域。然而，我们没有发现证据表明，人类患者内部结构域的突变会影响ZASP/Cypher与a-actinin的共同定位，或者这些突变会破坏ZASP/Cypher蛋白的稳定性。(C)2006 Elsevier Inc.保留所有权利。
Z-band alternatively spliced PDZ-containing protein (ZASP/Cypher) has an important role in maintaining Z-disc stability in striated and cardiac muscle. ZASP/Cypher interacts through its PDZ domain with the major Z-disc actin cross-linker, a-actinin. ZASP/Cypher also has a conserved sequence called the ZM-motif, and it is found in two alternatively spliced exons 4 and 6. We have shown earlier that the ZM-motif containing internal regions of two related proteins ALP and CLP36 interact with a-actinin rod region, and that the ZM-motif is important in targeting ALP to the a-actinin containing structures in cell. Here, we show that the ZASP/Cypher internal fragments containing either ZM exon 4 or 6 co-localized with alpha-actinin in cultured myoblasts and nonmuscle cells. Fragments of 130 residues around the ZM-consensus were sufficient for localization, which is similar to our previous results of ALP. Moreover, ZASP/Cypher protein interacted directly with the et-actinin rod and competed with ALP in binding to the rod. During the inhibition of stress fiber assembly ZASP/Cypher and a-actinin co-localization could be partially disturbed, suggesting that ZASP/Cypher is bound to a-actinin mainly when a-actinin is localizing in stress fibers. Many point mutations found in cardiomyopathy patients are located in the internal region of ZASP/Cypher. However, we found no evidence that human patient mutations in the internal domain would affect the ZASP/Cypher co-localization with a-actinin, or that the mutations would destabilize the ZASP/Cypher protein. (c) 2006 Elsevier Inc. All rights reserved.