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

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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.