Linker region of nebulin family members plays an important role in targeting these molecules to cellular structures

Linker region of nebulin family members plays an important role in targeting these molecules to cellular structures
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DOI:
10.1007/s00441-006-0305-2
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发表时间:
2007-02-01
影响因子:
3.6
通讯作者:
Moncman, Carole L.
Moncman, Carole L.
中科院分区:
生物学3区
文献类型:
--
作者:
Panaviene, Zivile;Moncman, Carole L.

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肌动蛋白结合蛋白的星云蛋白家族在细胞骨架动力学和肌动蛋白丝稳定性中起着重要作用。所有家族成员都是模块化蛋白,其关键的定义结构特征是存在35个残基的星云蛋白模块。家族成员现在包括nebulin、nebulette、N-RAP、LASP-1和LIM-nebulette。Nebulin和neblette与横纹肌的细丝/Z线连接相关。LASP-1和LIM-nebulette在局灶性粘连中发现,N-RAP与肌肉细胞连接相关。虽然许多研究都集中在nebulin模块和肌动蛋白之间的相互作用的作用,这些蛋白质中的每一个都包含其他结构域,是必不可少的细胞靶向和功能。此前已证明,雾化团的富含丝氨酸的连接区正是通过靶向培养的心肌细胞中星云蛋白模块与心脏Z线的结合来达到这样的目的。在这份报告中,我们分析了LASP-1和LIM-neblette的同源区域在其纳入局灶性粘连中的靶向功能。我们已经发现LASP-1的接头区域对于其细胞定位确实是重要的,并且LIM-nebulette的缩短的接头区域驱动了nebulin模块与粘着斑的缔合。
The nebulin family of actin-binding proteins plays an essential role in cytoskeletal dynamics and actin filament stability. All of the family members are modular proteins with their key defining structural feature being the presence of the 35-residue nebulin modules. The family members now include nebulin, nebulette, N-RAP, LASP-1, and LIM-nebulette. Nebulin and nebulette are associated with the thin filament/Z-line junction of striated muscle. LASP-1 and LIM-nebulette are found within focal adhesions, and N-RAP is associated with muscle cellular junctions. Although much investigation has focused on the role of the interactions between nebulin modules and actin, each of these proteins contains other domains that are essential for their cellular targeting and functions. The serine-rich linker region of nebulette has previously been shown to serve just such a purpose by targeting the association of the nebulin modules to the cardiac Z-line in cultured cardiomyocytes. In this report, we analyze the targeting functions of the homologous regions of LASP-1 and LIM-nebulette in their incorporation into focal adhesions. We have found that the linker region of LASP-1 is indeed important for its cellular localization and that the shortened linker region of LIM-nebulette drives the association of nebulin modules to focal adhesions.