Analysis of P5B ATPase Function

• Applicant: Privatdozent Dr. Eric Lambie
• Subject Area: Developmental Biology ; Cell Biology
• Term: from 2014 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 257149307

Members of the P-type ATPase family of transmembrane transporters are found in all living organisms. Within eukaryotes, these proteins are grouped into five subfamilies, with the P5 subfamily the least well-characterized. Representatives of the two P5 subgroups, P5A and P5B, are present in eukaryotes ranging from yeast to humans. Mutations in two of the four human P5B ATPase genes have been implicated in neurodegenerative and neurodevelopmental disorders; however, the biological functions of these proteins, and the identities of their transport substrates remain elusive. We propose to use the nematode, Caenorhabditis elegans as a model to systematically examine the biological, physiological and biochemical functions of the P5B ATPases. The C. elegans genome encodes three P5B ATPases, CATP-5, CATP-6 and CATP-7. We isolated mutations in catp-6 during a genetic screen designed to identify genes that regulate Mg2+ homeostasis, whereas other researchers have published evidence that CATP-5 might act as a polyamine transporter. No characterization of CATP-7 has been reported. We plan to use forward and reverse genetic analyses, in combination with high-resolution imaging of living and fixed specimens, to determine when and where CATP-5 and CATP-6 are expressed, whether they possess identical transport activities, and whether direct interactions with other proteins are important for their in vivo regulation and function. We will also conduct in vitro experiments using isolated yeast vacuoles to directly test biochemical models for P5B ATPase function. We anticipate that the results of the proposed studies will be directly relevant to the functions of P5B ATPases in all organisms.

• DFG Programme: Research Grants