Disease relevance of Ptdss2

• In both M.9.1.1 and hepatoma cells transfected with PSS2 cDNA the rate of synthesis of PtdSer and PtdSer-derived PtdEtn did not exceed that in parental CHO cells or control McArdle cells respectively, in contrast to cells expressing similar levels of murine PSS1 [1].

High impact information on Ptdss2

• As judged by Northern blots, the expression of Pss1 was not up-regulated in Pss2-deficient cells and tissues [2].
• We conclude that Pss2 is responsible for the majority of serine exchange activity in in vitro assays, but a deficiency in this enzyme does not cause perturbations in phospholipid content or severe developmental abnormalities [2].
• The ability of testis extracts from Pss2-deficient mice to catalyze serine exchange was reduced by more than 95%; reductions of approximately 90% were noted in the brain and liver [2].
• Testis weight was reduced in Pss2-deficient mice, and some of the male mice were infertile [2].
• Histologic studies of Pss2-deficient mice revealed very high levels of beta-galactosidase expression in Sertoli cells of the testis and high levels of expression in brown fat, neurons, and myometrium [2].

Biological context of Ptdss2

• Whether Pss1 and Pss2 are both required for mammalian growth and development is not known, and no data exist on the relative contributions of the two enzymes to serine exchange activities in different tissues [2].
• Since the amino acid sequences of PSS1 and PSS2 are only approximately 30% identical, it is likely that they are encoded by different genes [3].
• Phospholipid homeostasis in phosphatidylserine synthase-2-deficient mice [4].

Anatomical context of Ptdss2

• We have now cloned and stably expressed a murine PSS2 cDNA in McArdle cells and M.9.1.1 cells [which are ethanolamine-requiring mutant Chinese hamster ovary (CHO) cells defective in PSS1] [1].

Associations of Ptdss2 with chemical compounds

• Since the ER contains serine and ethanolamine exchange activities, we had predicted that PSS2 would account for the serine exchange activity in the ER [5].
• In general agreement with the levels of mRNA expression, the choline exchange activity (contributed by PSS1, but not PSS2) was highest in brain, whereas serine and ethanolamine exchange activities were highest in testis and kidney [3].
• Phosphatidylserine (PtdSer) is synthesized in mammalian cells by two base-exchange enzymes: PtdSer synthase (PSS)-1 primarily uses phosphatidylcholine as a substrate for exchange with serine, whereas PSS2 uses phosphatidylethanolamine (PtdEtn) [1].
• Moreover, expression of murine PSS2 in McArdle cells did not inhibit PtdEtn synthesis via the CDP-ethanolamine pathway, whereas expression of similar levels of PSS1 activity inhibited this pathway by approx. 50% [1].

Analytical, diagnostic and therapeutic context of Ptdss2

• According to reverse transcriptase-mediated polymerase chain reaction, PSS1 and PSS2 mRNAs were expressed in all murine tissues examined [3].
• Unexpectedly, using immunoblotting experiments, we found that (i) PSS2 of CHO-K1 cells is present only in MAM and (ii) PSS2 is restricted to MAM of McArdle cells expressing recombinant PSS2 [5].

References