- 期刊
- OpenAccess
Nebulin: Structure, Function, and Disease in Striated Muscle
Nebulin在橫紋肌的構造、功能和疾病
摘要
Nebulin為一個巨大的肌原纖維蛋白質，繼肌凝蛋白、肌動蛋白、titin之後，nebulin形成橫紋肌的第四肌絲系統。單一nebulin分子自Z盤至細肌絲末端而纏繞整個細肌絲的全長。Nebulin包含獨特的酸性區域、由35個氨基酸形成組件複本構造、鍊環區域以及src homologous (SH3)區域。Nebulin主要功能為扮演細肌絲長度的獨特性調節者，肌凝蛋白與肌動蛋白滑動之不可或缺的調控者，以及訊息傳遞的生物分子成應者。Nebulin基因突變是細棒狀肌病(nemaline myopathies)的病因，此病呈現在Z盤nebulin的SH3區域缺損情形。基於病理學上的相似性，一些骨骼肌疾病皆可觀察到nebulin降減的現象，例如棄用型萎縮症、Duchenne肌失養症、運動造成肌肉損傷以及過度酒精攝取而導致肌肉病變等。除了nebulette和nebulin相關支撐蛋白(N-RAP)外，許多證據支持在脊髓動物的心臟存有心肌nebulin。本文綜合最近文獻以期望提供學理基礎而記述nebulin的多種面貌。
並列摘要
Nebulin is a giant myofibri1lar protein (600-900 kDa) and forms the fourth filament system in striated sarcomeres. Single nebulin molecules span the entire length of the thin filament from the Z-disc to the thin filament pointed ends. Nebulin consists of an acidic domain, 35-residue modular repeats, a linker domain, and a Src homologous (SH3) domain. The major function of nebulin is to act as a unique regulator of thin filament length, a vital modulator of actomyosin sliding, and a biomolecular sensor of signal transduction. Mutation in the nebulin gene is a disease-causing factor of nemaline myopathies, and this case report presents a specific loss of the nebulin's SH3 domain in the Z-disc. Based on pathological similarities, it seems that the nebulin decline exists in some skeletal muscle diseases, such as disuse atrophy, Duchenne muscular dystrophy (DMD), exercise-induced muscle damage, and myopathies of excessive alcohol consumption. In addition to nebulette and the nebulin-related anchoring protein (N-RAP), there are numerous data supporting that cardiac nebulin is expressed in vertebrate hearts. Taken together, this article aims to summarize recent studies in the hopes of improving the knowledge base of various aspects of nebulin.