Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Testis- and sperm-specific protein phosphatase, PP1gamma2, is a key enzyme regulating sperm function. Its activity decreases during sperm maturation in the epididymis. Inhibition of PP1gamma2 leads to motility initiation and stimulation. Our laboratory is focused on identifying mechanisms responsible for the decline in PP1gamma2 activity during sperm motility initiation in the epididymis. Previously, using immuno-affinity chromatography, we showed that a mammalian homologue of yeast sds22 is bound to PP1gamma2 in motile caudal spermatozoa (Huang Z, et al. Biol Reprod 2002; 67:1936-1942). The objectives of this study were to determine: 1) stoichiometry of PP1gamma2-sds22 binding and 2) whether PP1gamma2 in immotile caput epididymal spermatozoa is bound to sds22. The enzyme from caudal and caput sperm extracts was purified by column chromatography. Immunoreactive PP1gamma2 and sds22 from both caudal and caput spermatozoa were found in the flow-through fraction of a DEAE-cellulose column. However, PP1gamma2 from caudal spermatozoa was inactive, whereas in caput spermatozoa it was active. The DEAE-cellulose flow-through fractions were next passed through a SP-sepharose column. Caudal sperm sds22 and PP1gamma2 coeluted in the gradient fraction. In contrast, caput sperm sds22 and PP1gamma2 were separated in the flow-through and gradient fractions, respectively. Further purification through a Superose 6 column showed that PP1gamma2-sds22 complex from caudal sperm was 88 kDa in size. Caput sperm sds22 and PP1gamma2 eluted at 60 kDa and 39 kDa, respectively. SDS-PAGE of these purified fractions revealed that in caudal sperm, the 88-kDa species is composed of sds22 (43 kDa) and PP1gamma2 (39 kDa), suggesting a 1:1 complex between these two proteins. PP1gamma2 bound to sds22 in this complex was inactive. Caput sperm sds22 eluting as a 60-kDa species was found to be associated with a 17-kDa protein (p17). This suggests that dissociation of sds22 from p17 or some other posttranslational modification of sds22 is required for its binding and inactivation of PP1gamma2. Studies are currently underway to determine the mechanisms responsible for development of sds22 binding to PP1gamma2 during epididymal sperm maturation.
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PMID:Binding and inactivation of the germ cell-specific protein phosphatase PP1gamma2 by sds22 during epididymal sperm maturation. 1282 76

The intracellular mediators cyclic AMP, calcium and pH regulate sperm function through changes in protein phosphorylation. Protein phosphorylation is the net result of the actions of protein kinases and phosphatases. The protein phosphatase isoform, PPlgamma2, with a unique C-terminus extension is highly enriched in spermatozoa and testis. Changes in PPlgamma2 catalytic activity, its phosphorylation, and binding to its regulatory proteins change during epididymal maturation. Thus PPgamma2 is a key protein in sperm motility regulation; decreased enzyme activity is associated with increased motility. This review summarizes the current knowledge of this sperm protein phosphatase. The biochemical properties of its regulatory proteins, sds22 and protein 14-3-3, among others, are discussed. Future studies will elucidate sperm signalling pathways involving PP1gamma2 and determine if the unique structure of PP1gamma2 is critical to normal male gamete development and function. Understanding the role of PP1gamma2 will not only contribute to the basic understanding of male gamete functions but also has practical applications in clinical andrology and in the development of male contraceptives.
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PMID:Regulation of sperm function by protein phosphatase PP1gamma2. 1756 66

Mammalian spermatozoa acquire the capacity for motility and fertilization during the transit through the epididymis under the control of different factors, such as cAMP, intracellular pH, intracellular calcium and phosphorylation of sperm proteins. As the acquisition of functional competence including gaining motility during epididymal transit occurs in the complete absence of contemporaneous gene transcription and translation on the part of the spermatozoa, it is widely accepted that post-translational modifications are the only means by which spermatozoa can acquire functionality. Serine-threonine protein phosphatase 1 (PP1) together with their testis/sperm-specific interacting proteins might be involved in this regulatory mechanism. PP1alpha, PP1beta/delta, PP1gamma1 and PP1gamma2 are all expressed in the testis whereas PP1gamma2 is the only isoform expressed on spermatozoa. I2, I3, sds22, 14-3-3 and hsp90 are associated with PP1gamma2 in spermatozoa located on the sperm head and tail. Activity of PP1gamma2 and the binding pattern to these regulatory proteins changes in spermatozoa recruited from the caput and those from the cauda part of the epididymis. In this review, we summarize the possible roles of PP1 on spermatozoa during spermatogenesis and flagellar motility control. We suggest that PP1 might take part in the inhibition of the sperm motility activation by interacting with AKAPs and CAMKII. A hypothesized signaling pathway of mammalian sperm motility activation and PP1's function has been proposed.
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PMID:Role(s) of the serine/threonine protein phosphatase 1 on mammalian sperm motility. 1785 41