Functional characterization of novel mechanisms regulating SERCA activity and Ca2+ homeostasis in D. melanogaster (P21*)

P21项目的重点是从机制上了解苍蝇肌浆网钙吸收膜微域中调节钙ATPase(SERCA)活性的新过程。金属蛋白酶NEP4活性受损显著影响心肌细胞内钙稳态，并诱发强烈的心律失常表型。为了了解NEP4介导的SERCA调控的分子机制，他们将(1)鉴定与表型相关的NEP4肽底物，(2)分析细胞器下层的定位，(3)详细确定NEP4和SERCA之间的功能和动力学。

The project P21 focuses on the mechanistic understanding of a novel process that regulates activity of the calcium ATPase (SERCA) within Ca2+ uptake membrane microdomains of the sarcoplasmic reticulum of flies. Impaired activity of the metalloprotease Nep4 significantly affected cardiac Ca2+ homeostasis and induced a strong arrhythmia phenotype. To understand the molecular mechanisms underlying the Nep4 mediated regulation of SERCA, they will (i) identify phenotype-relevant Nep4 peptide substrates, (ii) analyze the suborganellar localization, and (iii) determine the funciton and dynamics between Nep4 and SERCA in detail.