Tissue-specific functional studies on calpains

2014 Fiscal Year Final Research Report

• Project/Area Number: 23247021
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: SORIMACHI Hiroyuki 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 分野長 (10211327)
• Co-Investigator(Renkei-kenkyūsha): ONO Yasuko 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主席研究員 (20392376) ; HATA Shoji 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主席研究員 (10392375) ; MATSUOKA Kunie 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 主席研究員 (40291158) ; TONAMI Kazuo 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 研究員 (70511393)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: カルパイン / プロテオリシス / 質量分析 / 筋ジストロフィー / 胃腸疾患 / 自己消化 / 酵素学 / 基質特異性

Outline of Final Research Achievements

Calpains (CAPNs) are intracellular proteases that modulate substrate proteins by limited proteolysis. Although CAPN1/2 have well been studied so far, their physiological functions are still elusive because of their ubiquitous expression profiles.We have identified several tissue-specific calpains, and analyzed their functions in relation to the functions of the tissues where they are expressed. As a result, we revealed that defects of CAPN3 proteolytic activity cause muscular dystrophy, and that deficiencies of CAPN8/9 result in stress-induced gastric ulcer. Furthermore, other tissue-specific calpains were analyzed in terms of tissue functions. Proteomic analysis suggested that several novel substrates of these new members of calpains play important roles on pathophysiology of calpain-deficient diseases, "calpainopathies".

Free Research Field

分子生化学