Isolation and characterization of mammalian glycerophosphodiester phosphodiesterases

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Bacterial glycerophosphodiester phosphodiesterases are well-characterized to be periplasmic and cytosolic proteins, which play a critical role in the hydrolysis of deacylated glycerophospholipids to glycerol phosphate and alcohol. In contrast, two novel mammalian GP-PDEs, GDE1 and GDE3, were recently identified, and were shown to be involved in several physiological functions.1. A GP-PDE homolog, GDE2, was widely expressed in brain tissues including, and that the expression of GDE2 in neuroblastoma Neuro2A cells was significantly up-regulated during neuronal differentiation by retinoic acid (RA) treatment. Stable expression of GDE2 resulted in neurite formation in the absence of RA, and GDE2 accumulated at the regions of perinuclear and growth cones in Neuro2A cells. Furthermore, a loss-of-function of GDE2 in Neuro2A cells by RNAi blocked RA-induced neurite formation. These results demonstrate that GDE2 expression during neuronal differentiation plays an important role for growing neurites.2. In this study, seven mammalian GP-PDEs were virtually cloned by the approach using bioinformatics. Analysis of the hydrophobicity profile of a novel GDE, GDE7, protein indicated that two distinct hydrophobic regions are located at the N-terminus and at the C-terminus. GDE7 was expressed in mouse skin, and might be involved in the maintenance of keratinocytes.3. The predicted protein sequence of GDE5 does not contain any transmembrane sequence, suggesting that GDE5 functions as a cytosolic protein. Expression of GDE5 mRNA was shown to be regulated in skeletal muscles of fasted mice and diabetic KK-Ay mice, but its functions in skeletal muscle have remained poorly understood. In this study, I created transgenic mice specifically overexpressing GDE5 in skeletal muscle. These mice had a reduced skeletal muscle mass. Microarray analysis revealed that the expression of several genes related to cellular stress was increased in skeletal muscles of transgenic mice.