Extracellular Function of Multiple Inositol Polyphosphate Phosphatase in the Drosophila Trachea

multiple inositol polyphosphate phosphatase;mipp;trachea;inositol phosphate;filopodia;FGF;migration;Biology

Cheng, Yim LingDevreotes, Peter N. ;

Johns Hopkins University

关键词: multiple inositol polyphosphate phosphatase;    mipp;    trachea;    inositol phosphate;    filopodia;    FGF;    migration;    Biology;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/39346/CHENG-DISSERTATION-2015.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Inositol polyphosphates (IPs) are important second messengers involved in diverse cellular processes. Inositol is a cyclohexane with six hydroxyl groups, which can be phosphorylated to generate inositol polyphosphates. Variation in the number and combination of phosphorylated positions on the inositol generates a wide array of inositol polyphosphates. It was generally known that IPs exist and function in the cytoplasm. The discovery of the nuclear localization of IPs enzymes opened up investigations on the role of nuclear pools of IPs and revealed an involvement in gene regulation and mRNA export. IP6 is highly abundant in nature, and organisms accumulate extracellular IP6 through their diet. Whereas IP6 can be internalized into cells, a large percentage of IP6 remains in the extracellular space. The functions of the extracellular IPs remain unknown.Mipp (Multiple Inositol Polyphosphate Phosphatase) is a highly conserved histidine phosphatase and is a major phosphatase that dephosphorylates higher order IPs (IP6 to IP4) to IP3. Mammalian Mipp has an unusual cellular localization - the ER lumen. Importantly, there is no overt phenotype in mipp loss-of-function mice. Thus, studies on Mipp function remain at a standstill. We observed Drosophila Mipp1 to be highly and dynamically expressed in the embryonic trachea. We further discovered Mipp1 functions on the cell surface to facilitate filopodia formation to drive migration and elongation of the tracheal branches. Our findings revealed that Mipp1 dephosphorylates extracellular IPs and that Mipp1 phosphatase activity is required for its function in the trachea. Further investigation on the role of each specific extracellular IP and its extracellular interactors will provide additional insight on the functions of the extracellular IPs.