Research ArticleFertility

Dephosphorylation of protamine 2 at serine 56 is crucial for murine sperm maturation in vivo

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Science Signaling  26 Mar 2019:
Vol. 12, Issue 574, eaao7232
DOI: 10.1126/scisignal.aao7232

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Protamine dephosphorylation for fertility

During the final stage of spermatogenesis, protamines tightly package DNA in the mature sperm. Itoh et al. generated mice deficient in the heat shock protein and chaperone Hspa4l, which is implicated in spermatogenesis. The mice were infertile with malformed sperm heads, a phenotype similar to that of mice deficient in the phosphatase Ppp1cc2. The authors showed that Hspa4l was required to release Ppp1cc2 from a complex with other chaperones, enabling its translocation to chromatin. In vitro studies showed that Ppp1cc2 dephosphorylated protamine 2 at Ser56. Expression of the unphosphorylatable protamine 2 S56A mutant reversed the infertility of Hspa4l-deficient mice, suggesting that the dephosphorylation of protamine 2 at Ser56 is important for its role in sperm maturation.

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