The functional role of ahnak in skeletal muscle fibers in an ahnak knock-out-mouse model

ahnak 在 ahnak 敲除小鼠模型中骨骼肌纤维的功能作用

• 批准号: 47203272
• 负责人: Professor Dr. Ingo Morano
• 金额: --
• 依托单位: Max-Delbrück-Centrum für Molekulare Medizin (MDC) in der Helmholtz-Gemeinschaft
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/47203272?language=en
• 关键词: functional; role; ahnak; skeletal; muscle

Ahnak is a muscle protein that may be involved in plasmalemma enlargement and membrane repair. The aim of the proposed project is the elucidation of ahnak's role in skeletal muscle cells and tissue. Recently, we demonstrated that in cardiomyocytes ahnak is associated with the regulation of the L-Type Ca2+ channel activity and therefore, excitation-contraction coupling, as well as the cell's structural integrity. However, the functional role of ahnak in skeletal muscle is unclear. Preliminary results suggest that skeletal muscle atrophy induced by denervation significantly upregulated ahnak expression. Therefore, we will first identify ahnak interaction partners in skeletal muscle, in particular the L-type Ca2+ channel and dysferltn, by immuno-precipitation and MALDI-TOFF analysis. Second, we will analyze the functional role of ahnak using a homozygous ahnak gene-deficient mouse model (contraction and intracellular Ca2+ in skeletal muscle registration of intact single skeletal muscle fibers from Flexor digitorum brevis of mouse hindlimb). Third, we wili analyze the functional (simultaneous registration of contraction and intracellular Ca2+) and structural (electron microscopy) role of ahnak in atrophic muscle induced by hindlimb immobilization of normal and ahnak gene-deficient mice.

Ahnak是一种肌肉蛋白，可能参与质膜扩大和膜修复。该项目的目的是阐明ahnak在骨骼肌细胞和组织中的作用。最近，我们证明了在心肌细胞中，ahnak与L型Ca 2+通道活性的调节相关，因此，兴奋-收缩偶联以及细胞的结构完整性。然而，ahnak在骨骼肌中的功能作用尚不清楚。初步结果表明，骨骼肌萎缩引起的失神经支配显着上调ahnak的表达。因此，我们将首先通过免疫沉淀和MALDI-TOFF分析鉴定骨骼肌中的ahnak相互作用伴侣，特别是L型Ca 2+通道和dysferltn。其次，我们将使用纯合ahnak基因缺陷小鼠模型（小鼠后肢趾短屈肌完整单骨骼肌纤维的骨骼肌收缩和细胞内Ca 2+配准）分析ahnak的功能作用。第三，我们将分析的功能（收缩和细胞内Ca 2+的同时注册）和结构（电子显微镜）的作用，ahnak在萎缩的肌肉引起的后肢制动正常和ahnak基因缺陷小鼠。