Protein Kinase D regulates several aspects of development in Drosophila melanogaster
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Protein Kinase D (PKD) is an effector of diacylglycerol-regulated signaling pathways. Three isoforms are known in mammals that have been linked to diverse cellular functions including regulation of cell proliferation, differentiation and motility as well as secretory transport from the trans-Golgi network to the plasma membrane. In Drosophila, there is a single PKD orthologue, whose broad expression implicates a more general role in development.
We have employed tissue specific overexpression of various PKD variants as well as RNAi mediated depletion, in order to investigate the function of the PKD gene in Drosophila. Apart from a wild type, a presumptive kinase dead (kd) and constitutively active (SE) Drosophila PKD variant, we also analyzed two human isoforms hPKD2 and hPKD3 for their capacity to substitute PKD activity in the fly. Overexpression of either wild type or kd PKD variants affected primarily wing vein development. However, overexpression of SE-PKD was deleterious as was depletion of PKD by RNAi. We observed tissue loss, wing defects and degeneration of the retina. The latter phenotype conforms to a role of PKD in the regulation of cytoskeletal dynamics. Strongest phenotypes were larval to pupal lethality. RNAi induced phenotypes could be rescued by a concurrent overexpression of either wild type or SE-PKD. Most interestingly, rescue was observed with both human isoforms hPKD2 and hPKD3.
Our data are compatible with the hypothesis that in Drosophila PKD is a multifunctional kinase similar to vertebrates that is involved in diverse processes such as regulation of the cytoskeleton, cell proliferation and death as well as differentiation of various fly tissues.
Source: BMC Developmental Biology. June 2007
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