Regulators of the protein phosphatase PP1γ2, PPP1R2, PPP1R7, and PPP1R11 are involved in epididymal sperm maturation. Issue 3 (25th August 2018)

• Record Type: Journal Article
• Authors: Goswami, Suranjana; Korrodi‐Gregório, Luís; Sinha, Nilam; Bhutada, Sumit; Bhattacharjee, Rahul; Kline, Douglas; Vijayaraghavan, Srinivasan
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 3(2019:Mar.)
• Page Start: 3105
• Page End: 3118
• Publication Date: 2018-08-25
• Subjects: inhibitor‐2 (I2) -- inhibitor‐3 (I3) -- PP1γ2 -- PPP1R11 -- PPP1R17 -- PPP1R2 -- sds22 -- sperm -- spermatogenesis, testis; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.27130
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: The serine/threonine protein phosphatase 1 (PP1) inhibitors PPP1R2, PPP1R7, and PPP1R11 are evolutionarily ancient and highly conserved proteins. Four PP1 isoforms, PP1α, PP1β, PP1γ1, and PP1γ2, exist; three of them except PP1γ2 are ubiquitous. The fact that PP1γ2 isoform is present only in mammalian testis and sperm led to the notion that isoform‐specific regulators for PP1γ2 in sperm may be responsible for its function. In this report, we studied these inhibitors, PPP1R2, R7, and R11, to determine their spatial and temporal expression in testis and their regulatory functions in sperm. We show that, similar to PP1γ2, the three inhibitors are expressed at high levels in developing spermatogenic cells. However, the transcripts for the regulators are expressed as unique sizes in testis compared with somatic tissues. The three regulators share localization with PP1γ2 in the head and the principal piece of sperm. We show that the association of inhibitors to PP1γ2 changes during epididymal sperm maturation. In immotile caput epididymal sperm, PPP1R2 and PPP1R7 are not bound to PP1γ2, whereas in motile caudal sperm, all three inhibitors are bound as heterodimers or heterotrimers. In caudal sperm from male mice lacking sAC and glycogen synthase kinase 3, where motility and fertility are impaired, the association of PP1γ2 to the inhibitors resembles immature caput sperm. Changes in the association of the regulators with PP1γ2, due to their phosphorylation, are part of biochemical mechanisms responsible for the development of motility and fertilizing ability of sperm during their passage through the epididymis. Abstract : We have shown the changes in the association of PP1γ2 with its regulators occur during sperm maturation in the epididymis. These changes were shown to occur in both bovine and mouse epididymal sperm. The alteration in binding of the regulators are due to changes in their phosphorylation. This study, for the first time, lays the basis for the long‐sought understanding of the biochemical mechanisms underlying sperm maturation in the epididymis.