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Publication : Dependence of sperm structural and functional integrity on testicular calcineurin isoform PPP3R2 expression.

First Author  Liu Y Year  2020
Journal  J Mol Cell Biol Volume  12
Issue  7 Pages  515-529
PubMed ID  31900494 Mgi Jnum  J:299001
Mgi Id  MGI:6489634 Doi  10.1093/jmcb/mjz115
Citation  Liu Y, et al. (2020) Dependence of sperm structural and functional integrity on testicular calcineurin isoform PPP3R2 expression. J Mol Cell Biol 12(7):515-529
abstractText  After leaving the testis, mammalian sperm undergo a sequential maturation process in the epididymis followed by capacitation during their movement through the female reproductive tract. These phenotypic changes are associated with modification of protein phosphorylation and membrane remodeling, which is requisite for sperm to acquire forward motility and induce fertilization. However, the molecular mechanisms underlying sperm maturation and capacitation are still not fully understood. Herein, we show that PPP3R2, a testis-specific regulatory subunit of protein phosphatase 3 (an isoform of calcineurin in the testis), is essential for sperm maturation and capacitation. Knockout of Ppp3r2 in mice leads to male sterility due to sperm motility impairment and morphological defects. One very noteworthy change includes increases in sperm membrane stiffness. Moreover, PPP3R2 regulates sperm maturation and capacitation via (i) modulation of membrane diffusion barrier function at the annulus and (ii) facilitation of cholesterol efflux during sperm capacitation. Taken together, PPP3R2 plays a critical role in modulating cholesterol efflux and mediating the dynamic control of membrane remodeling during sperm maturation and capacitation.
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