OALib Journal期刊
ISSN: 2333-9721
费用：99美元

投递稿件

查看量	下载量

相关文章
更多...

PLOS ONE 2013

Dissociation between AKAP3 and PKARII Promotes AKAP3 Degradation in Sperm Capacitation

DOI: 10.1371/journal.pone.0068873

Pnina Hillman, Debby Ickowicz, Ruth Vizel, Haim Breitbart

Full-Text Cite this paper Add to My Lib

Abstract:

Ejaculated spermatozoa must undergo a series of biochemical modifications called capacitation, prior to fertilization. Protein-kinase A (PKA) mediates sperm capacitation, although its regulation is not fully understood. Sperm contain several A-kinase anchoring proteins (AKAPs), which are scaffold proteins that anchor PKA. In this study, we show that AKAP3 is degraded in bovine sperm incubated under capacitation conditions. The degradation rate is variable in sperm from different bulls and is correlated with the capacitation ability. The degradation of AKAP3 was significantly inhibited by MG-132, a proteasome inhibitor, indicating that AKAP3 degradation occurs via the proteasomal machinery. Treatment with Ca2+-ionophore induced further degradation of AKAP3; however, this effect was found to be enhanced in the absence of Ca2+ in the medium or when intracellular Ca2+ was chelated the degradation rate of AKAP3 was significantly enhanced when intracellular space was alkalized using NH4Cl, or when sperm were treated with Ht31, a peptide that contains the PKA-binding domain of AKAPs. Moreover, inhibition of PKA activity by H89, or its activation using 8Br-cAMP, increased AKAP3 degradation rate. This apparent contradiction could be explained by assuming that binding of PKA to AKAP3 protects AKAP3 from degradation. We conclude that AKAP3 degradation is regulated by intracellular alkalization and PKARII anchoring during sperm capacitation.

References

[1]	Yanagimachi R, Knobil E, Neil JD (1994) Mammalian fertilization. The Physiology of Reproduction. New York: Raven Press. pp. 189-317.
[2]	Naz RK, Ahmad K, Kumar R (1991) Role of membrane tyrosine proteins in human spermatozoa function. J Cell Sci 99: 157-165. PubMed: 1721918.
[3]	Visconti PE, Moore GD, Bailey JL, Leclerc P, Connors SA et al. (1995) Capacitation of mouse spermatozoa. II. Protein tyrosine phosphorylation and capacitation are regulated by a cAMP-dependent pathway. Development 121: 1139-1150. PubMed: 7538069.
[4]	Harrison DA, Carr DW, Meizel S (2000) Involvement of protein kinase A and A kinase anchoring protein in the progesterone-initiated human sperm acrosome reaction. Biol Reprod 62: 811-820. doi:10.1095/biolreprod62.3.811. PubMed: 10684828.
[5]	Corbin JD, Soderling TR, Park CR (1973) Regulation of adenosine 3',5'-monophosphate-dependent protein kinase. I. Preliminary characterization of the adipose tissue enzyme in crude extracts. J Biol Chem 248: 1813-1821. PubMed: 4348550.
[6]	Kim C, Xuong NH, Taylor SS (2005) Crystal structure of a complex between the catalytic and regulatory (RIalpha) subunits of PKA. Science 307: 690-696. doi:10.1126/science.1104607. PubMed: 15692043.
[7]	Kim C, Cheng CY, Saldanha SA, Taylor SS (2007) PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activation. Cell 130: 1032-1043. doi:10.1016/j.cell.2007.07.018. PubMed: 17889648.
[8]	Niu J, Vaiskunaite R, Suzuki N, Kozasa T, Carr DW et al. (2001) Interaction of heterotrimeric G13 protein with an A-kinase-anchoring protein 110 (AKAP110) mediates cAMP-independent PKA activation. Curr Biol 11: 1686-1690. doi:10.1016/S0960-9822(01)00530-9. PubMed: 11696326.
[9]	Cohen G, Rubinstein S, Gur Y, Breitbart H (2004) Crosstalk between protein kinase A and C regulates phospholipase D and F-actin formation during sperm capacitation. Dev Biol 267: 230-241. doi:10.1016/j.ydbio.2003.10.034. PubMed: 14975729.
[10]	Breitbart H, Rubinstein S, Etkovitz N (2006) Sperm capacitation is regulated by the crosstalk between protein kinase A and C. Mol Cell Endocrinol 252: 247-249. doi:10.1016/j.mce.2006.03.019. PubMed: 16647197.
[11]	Etkovitz N, Rubinstein S, Daniel L, Breitbart H (2007) Role of PI3-kinase and PI4-kinase in actin polymerization during bovine sperm capacitation. Biol Reprod 77: 263-273. doi:10.1095/biolreprod.106.056705. PubMed: 17494916.
[12]	Wennemuth G, Carlson AE, Harper AJ, Babcock DF (2003) Bicarbonate actions on flagellar and Ca2+ -channel responses: initial events in sperm activation. Development 130: 1317-1326. doi:10.1242/dev.00353. PubMed: 12588848.
[13]	Carlson AE, Hille B, Babcock DF (2007) External Ca2+ acts upstream of adenylyl cyclase SACY in the bicarbonate signaled activation of sperm motility. Dev Biol 312: 183-192. doi:10.1016/j.ydbio.2007.09.017. PubMed: 17950270.
[14]	Shahar S, Wiser A, Ickowicz D, Lubart R, Shulman A et al. (2011) Light-mediated activation reveals a key role for protein kinase A and sarcoma protein kinase in the development of sperm hyper-activated motility. Hum Reprod 26: 2274-2282. doi:10.1093/humrep/der232. PubMed: 21771771.
[15]	Diviani D, Scott JD (2001) AKAP signaling complexes at the cytoskeleton. J Cell Sci 114: 1431-1437. PubMed: 11282019.
[16]	Michel JJ, Scott JD (2002) AKAP mediated signal transduction. Annu Rev Pharmacol Toxicol 42: 235-257. doi:10.1146/annurev.pharmtox.42.083101.13580？1. PubMed: 11807172.
[17]	Carnegie GK, Means CK, Scott JD (2009) A-kinase anchoring proteins: from protein complexes to physiology and disease. IUBMB Life 61: 394-406. doi:10.1002/iub.168. PubMed: 19319965.
[18]	Wong W, Scott JD (2004) AKAP signalling complexes: focal points in space and time. Nat Rev Mol Cell Biol 5: 959-970. doi:10.1038/nrm1527. PubMed: 15573134.
[19]	Dell’Acqua ML, Smith KE, Gorski JA, Horne EA, Gibson ES et al. (2006) Regulation of neuronal PKA signaling through AKAP targeting dynamics. Eur J Cell Biol 85: 627-633. doi:10.1016/j.ejcb.2006.01.010. PubMed: 16504338.
[20]	Fiedler SE, Bajpai M, Carr DW (2008) Identification and characterization of RHOA-interacting proteins in bovine spermatozoa. Biol Reprod 78: 184-192. doi:10.1095/biolreprod.107.062943. PubMed: 17928627.
[21]	Rawe VY, Ramalho-Santos J, Payne C, Chemes HE, Schatten G (2004) WAVE1, an A-kinase anchoring protein, during mammalian spermatogenesis. Hum Reprod 19: 2594-2604. doi:10.1093/humrep/deh513. PubMed: 15471936.
[22]	Reinton N, Collas P, Haugen TB, Skalhegg BS, Hansson V et al. (2000) Localization of a novel human A-kinase-anchoring protein, hAKAP220, during spermatogenesis. Dev Biol 223: 194-204. doi:10.1006/dbio.2000.9725. PubMed: 10864471.
[23]	Carr DW, Acott TS (1990) The phosphorylation of a putative sperm microtubule-associated protein 2 (MAP2) is uniquely sensitive to regulation. Biol Reprod 43: 795-805. doi:10.1095/biolreprod43.5.795. PubMed: 1705444.
[24]	Carr DW, Newell AE (2007) The role of A-kinase anchoring proteins (AKaps) in regulating sperm function. Soc Reprod Fertil Suppl 63: 135-141. PubMed: 17566268.
[25]	Lea IA, Widgren EE, O’Rand MG (2004) Association of sperm protein 17 with A-kinase anchoring protein 3 in flagella. Reprod Biol Endocrinol 2: 57. doi:10.1186/1477-7827-2-57. PubMed: 15257753.
[26]	Miki K, Willis WD, Brown PR, Goulding EH, Fulcher KD et al. (2002) Targeted disruption of the Akap4 gene causes defects in sperm flagellum and motility. Dev Biol 248: 331-342. doi:10.1006/dbio.2002.0728. PubMed: 12167408.
[27]	Fiedler SE, Dudiki T, Vijayaraghavan S, Carr DW (2013) Loss of R2D2 proteins ROPN1 and ROPN1L causes defects in murine sperm motility, phosphorylation, and fibrous sheath integrity. Biol Reprod 88: 41. doi:10.1095/biolreprod.112.105262. PubMed: 23303679.
[28]	Luconi M, Carloni V, Marra F, Ferruzzi P, Forti G et al. (2004) Increased phosphorylation of AKAP by inhibition of phosphatidylinositol 3-kinase enhances human sperm motility through tail recruitment of protein kinase A. J Cell Sci 117: 1235-1246. doi:10.1242/jcs.00931. PubMed: 14996943.
[29]	Parrish JJ, Susko-Parrish JL, Graham JK (1999) In vitro capacitation of bovine spermatozoa: Role of intracellular calcium. Theriogenology 51: 461-472. doi:10.1016/S0093-691X(98)00240-4. PubMed: 10729105.
[30]	Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH et al. (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150: 76-85. doi:10.1016/0003-2697(85)90442-7. PubMed: 3843705.
[31]	Kong M, Diaz ES, Morales P (2009) Participation of the human sperm proteasome in the capacitation process and its regulation by protein kinase A and tyrosine kinase. Biol Reprod 80: 1026-1035. doi:10.1095/biolreprod.108.073924. PubMed: 19144957.
[32]	Zimmerman S, Sutovsky P (2009) The sperm proteasome during sperm capacitation and fertilization. J Reprod Immunol 83: 19-25. doi:10.1016/j.jri.2009.07.006. PubMed: 19853307.
[33]	Rojas FJ, Brush M, Moretti-Rojas I (1999) Calpain-calpastatin: a novel, complete calcium-dependent protease system in human spermatozoa. Mol Hum Reprod 5: 520-526. doi:10.1093/molehr/5.6.520. PubMed: 10340998.
[34]	Cook SP, Babcock DF (1993) Activation of Ca2+ permeability by cAMP is coordinated through the PHi increase induced by speract. J Biol Chem 268: 22408-22413. PubMed: 7693668.
[35]	Garcia MA, Meizel S (1999) Regulation of intracellular pH in capacitated human spermatozoa by a Na+/H+ exchanger. Mol Reprod Dev 52: 189-195. doi:10.1002/(SICI)1098-2795(199902)52:2. PubMed: 9890750.
[36]	Schackmann RW, Chock PB (1986) Alteration of intracellular [Ca2+] i in sea urchin sperm by the egg peptide speract. J Biol Chem 261: 8719-8728. PubMed: 2424902.
[37]	Woo AL, James PF, Lingrel JB (2002) Roles of the Na,K-ATPase alpha4 isoform and the Na+/H+ exchanger in sperm motility. Mol Reprod Dev 62: 348-356. doi:10.1002/mrd.90002. PubMed: 12112599.
[38]	Rotman T, Etkovitz N, Spiegel A, Rubinstein S, Breitbart H (2010) Protein kinase A and protein kinase C(alpha)/PPP1CC2 play opposing roles in the regulation of phosphatidylinositol 3-kinase activation in bovine sperm. Reproduction 140: 43-56. doi:10.1530/REP-09-0314. PubMed: 20442273.
[39]	Chen Y, Cann MJ, Litvin TN, Iourgenko V, Sinclair ML et al. (2000) Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor. Science 289: 625-628. doi:10.1126/science.289.5479.625. PubMed: 10915626.
[40]	Vijayaraghavan S, Goueli SA, Davey MP, Carr DW (1997) Protein kinase A-anchoring inhibitor peptides arrest mammalian sperm motility. J Biol Chem 272: 4747-4752. doi:10.1074/jbc.272.8.4747. PubMed: 9030527.
[41]	Reinton N, Orstavik S, Haugen TB, Jahnsen T, Taskén K et al. (2000) A novel isoform of human cyclic 3',5'-adenosine monophosphate-dependent protein kinase, c alpha-s, localizes to sperm midpiece. Biol Reprod 63: 607-611. doi:10.1095/biolreprod63.2.607. PubMed: 10906071.
[42]	Zhang F, Hu Y, Huang P, Toleman CA, Paterson AJ et al. (2007) Proteasome function is regulated by cyclic AMP-dependent protein kinase through phosphorylation of Rpt6. J Biol Chem 282: 22460-22471. doi:10.1074/jbc.M702439200. PubMed: 17565987.
[43]	Galantino-Homer HL, Florman HM, Storey BT, Dobrinski I, Kopf GS (2004) Bovine sperm capacitation: assessment of phosphodiesterase activity and intracellular alkalinization on capacitation-associated protein tyrosine phosphorylation. Mol Reprod Dev 67: 487-500. doi:10.1002/mrd.20034. PubMed: 14991741.
[44]	Carr DW, Fujita A, Stentz CL, Liberty GA, Olson GE et al. (2001) Identification of sperm-specific proteins that interact with A-kinase anchoring proteins in a manner similar to the type II regulatory subunit of PKA. J Biol Chem 276: 17332-17338. doi:10.1074/jbc.M011252200. PubMed: 11278869.
[45]	Newell AE, Fiedler SE, Ruan JM, Pan J, Wang PJ et al. (2008) Protein kinase A RII-like (R2D2) proteins exhibit differential localization and AKAP interaction. Cell Motil Cytoskeleton 65: 539-552. doi:10.1002/cm.20279. PubMed: 18421703.
[46]	Bajpai M, Fiedler SE, Huang Z, Vijayaraghavan S, Olson GE et al. (2006) AKAP3 selectively binds PDE4A isoforms in bovine spermatozoa. Biol Reprod 74: 109-118. PubMed: 16177223.
[47]	Brener E, Rubinstein S, Cohen G, Shternall K, Rivlin J et al. (2003) Remodeling of the actin cytoskeleton during mammalian sperm capacitation and acrosome reaction. Biol Reprod 68: 837-845. PubMed: 12604633.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133