Lasp-2 expression, localization, and ligand interactions: A new Z-disc scaffolding protein

Lasp-2 expression, localization, and ligand interactions: A new Z-disc scaffolding protein
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DOI:
10.1002/cm.20244
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发表时间:
2008-01-01
影响因子:
--
通讯作者:
Gregorio, Carol C.
Gregorio, Carol C.
中科院分区:
其他
文献类型:
--
作者:
Zieseniss, Anke;Terasaki, Asako G.;Gregorio, Carol C.

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肌动蛋白结合蛋白的星云蛋白家族在包括横纹肌在内的多种细胞的肌动蛋白丝动力学中发挥着重要作用。我们在这里报告了一种新的横纹肌 Z 盘相关蛋白的鉴定:lasp-2(LIM 和 SH3 结构域蛋白-2)。 Lasp-2 是最近确定的星云蛋白家族成员。为了评估 lasp-2 在横纹肌中的作用,研究了鸡和小鼠组织以及鸡心脏和骨骼肌细胞的原代培养物中的 lasp-2 基因表达和定位。 Lasp-2 mRNA 早在鸡胚胎 25 阶段就被检测到,Lasp-2 蛋白与发育中的前肌原纤维结构、成熟肌原纤维的 Z 盘、粘着斑和培养心肌细胞的闰盘有关。 GFP 标记的 lasp-2 缺失构建体的表达表明,lasp-2 的 C 末端区域对于其在横纹肌细胞中的定位非常重要。 Lasp-2 将肌动蛋白丝组织成束,并直接与 Z 盘蛋白 α-肌动蛋白相互作用。这些结果与 lasp-2 作为横纹肌 Z 盘内支架和肌动蛋白丝组织蛋白的功能一致。
The nebulin family of actin-binding proteins plays an important role in actin filament dynamics in a variety of cells including striated muscle. We report here the identification of a new striated muscle Z-disc associated protein: lasp-2 (LIM and SH3 domain protein-2). Lasp-2 is the most recently identified member of the nebulin family. To evaluate the role of lasp-2 in striated muscle, lasp-2 gene expression and localization were studied in chick and mouse tissue, as well as in primary cultures of chick cardiac and skeletal myocytes. Lasp-2 mRNA was detected as early as chick embryonic stage 25 and lasp-2 protein was associated with developing pre-myofibril structures, Z-discs of mature myofibrils, focal adhesions, and intercalated discs of cultured cardiomyocytes. Expression of GFP-tagged lasp-2 deletion constructs showed that the C-terminal region of lasp-2 is important for its localization in striated muscle cells. Lasp-2 organizes actin filaments into bundles and interacts directly with the Z-disc protein alpha-actinin. These results are consistent with a function of lasp-2 as a scaffolding and actin filament organizing protein within striated muscle Z-discs.