Hostname: page-component-586b7cd67f-gb8f7 Total loading time: 0 Render date: 2024-11-24T18:43:18.119Z Has data issue: false hasContentIssue false
  • English
  • Français

Focal adhesion kinase PTK2 autophosphorylation is not required for the activation of sodium–hydrogen exchange by decreased cell volume in the preimplantation mouse embryo

Published online by Cambridge University Press:  07 June 2019

Jane C. Fenelon ,
Baozeng Xu  and
Jay M. Baltz Open the ORCID record for Jay M. Baltz [Opens in a new window]
Jane C. Fenelon
Affiliation:
Ottawa Hospital Research Institute, Ottawa, Ontario, Canada Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, and Department of Cellular and Molecular Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
Baozeng Xu
Affiliation:
Ottawa Hospital Research Institute, Ottawa, Ontario, Canada Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, and Department of Cellular and Molecular Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences, Changchun, China
Jay M. Baltz*
Affiliation:
Ottawa Hospital Research Institute, Ottawa, Ontario, Canada Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, and Department of Cellular and Molecular Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
*
*Address for correspondence: Jay M. Baltz. Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. Tel: +1 613 737 8899 ext. 79763. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Recovery from decreased cell volume is accomplished by a regulated increase of intracellular osmolarity. The acute response is activation of inorganic ion transport into the cell, the main effector of which is the Na+/H+ exchanger NHE1. NHE1 is rapidly activated by a cell volume decrease in early embryos, but how this occurs is incompletely understood. Elucidating cell volume-regulatory mechanisms in early embryos is important, as it has been shown that their dysregulation results in preimplantation developmental arrest. The kinase JAK2 has a role in volume-mediated NHE1 activation in at least some cells, including 2-cell stage mouse embryos. However, while 2-cell embryos show partial inhibition of NHE1 when JAK2 activity is blocked, NHE1 activation in 1-cell embryos is JAK2-independent, implying a requirement for additional signalling mechanisms. As focal adhesion kinase (FAK aka PTK2) becomes phosphorylated and activated in some cell types in response to decreased cell volume, we sought to determine whether it was involved in NHE1 activation in the early mouse embryo. FAK activity requires initial autophosphorylation of a tyrosine residue, Y397. However, FAK Y397 phosphorylation levels were not increased in either 1- or 2-cell embryos after cell volume was decreased. Furthermore, the selective FAK inhibitor PF-562271 did not affect NHE1 activation at concentrations that essentially eliminated Y397 phosphorylation. Thus, autophosphorylation of FAK Y397 does not appear to be required for NHE1 activation induced by a decrease in cell volume in early mouse embryos.

Keywords

Cell volumeEmbryoFocal adhesion kinaseNHE1Osmolarity
Type
Research Article
Information
Zygote , Volume 27 , Issue 3 , June 2019 , pp. 173 - 179
Copyright
© Cambridge University Press 2019 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alexander, RT and Grinstein, S (2006) Na+/H+ exchangers and the regulation of volume. Acta Physiol (Oxf) 187, 159–167.Google Scholar
Arold, ST (2011) How focal adhesion kinase achieves regulation by linking ligand binding, localization and action. Curr Opin Struct Biol 21, 808–813.Google Scholar
Aronson, PS, Nee, J and Suhm, MA (1982) Modifier role of internal H+ in activating the Na+-H+ exchanger in renal microvillus membrane vesicles. Nature 299, 161–163.Google Scholar
Arroyo, JP, Kahle, KT and Gamba, G (2013) The SLC12 family of electroneutral cation-coupled chloride cotransporters. Mol Aspects Med 34, 288–298.Google Scholar
Baltz, JM and Phillips, KP (1999) Intracellular ion measurements in single eggs and embryos using ion-sensitive fluorophores. In A Comparative Methods Approach to the Study of Oocytes and Embryos, ed. JD Richter, Oxford University Press, New York and Oxford, pp. 39–82.Google Scholar
Baltz, JM and Tartia, AP (2010) Cell volume regulation in oocytes and early embryos: connecting physiology to successful culture media. Hum Reprod Update 16, 166–176.Google Scholar
Baltz, JM and Zhou, C (2012) Cell volume regulation in mammalian oocytes and preimplantation embryos. Mol Reprod Dev 79, 821–831.Google Scholar
Dawson, KM and Baltz, JM (1997) Organic osmolytes and embryos: substrates of the Gly and beta transport systems protect mouse zygotes against the effects of raised osmolarity. Biol Reprod 56, 1550–1558.Google Scholar
Donowitz, M, Ming Tse, C and Fuster, D (2013) SLC9/NHE gene family, a plasma membrane and organellar family of Na+/H+ exchangers. Mol Aspects Med 34, 236–251.Google Scholar
Garnovskaya, MN, Mukhin, YV, Vlasova, TM and Raymond, JR (2003) Hypertonicity activates Na+/H+ exchange through Janus kinase 2 and calmodulin. J Biol Chem 278, 16908–16915.Google Scholar
Gatsios, P, Terstegen, L, Schliess, F, Häussinger, D, Kerr, IM, Heinrich, PC and Graeve, L (1998) Activation of the Janus kinase/signal transducer and activator of transcription pathway by osmotic shock. J Biol Chem 273, 22962–22968.Google Scholar
Gibb, CA, Poronnik, P, Day, ML and Cook, DI (1997) Control of cytosolic pH in two-cell mouse embryos: roles of H+-lactate cotransport and Na+/H+ exchange. Am J Physiol 273, C404–C419.Google Scholar
Hadi, T, Hammer, MA, Algire, C, Richards, T and Baltz, JM (2005) Similar effects of osmolarity, glucose, and phosphate on cleavage past the 2-cell stage in mouse embryos from outbred and F1 hybrid females. Biol Reprod 72, 179–187.Google Scholar
Harding, EA, Gibb, CA, Johnson, MH, Cook, DI and Day, ML (2002) Developmental changes in the management of acid loads during preimplantation mouse development. Biol Reprod 67, 1419–1429.Google Scholar
Hoffmann, EK and Pedersen, SF (2011) Cell volume homeostatic mechanisms: effectors and signalling pathways. Acta Physiol 202, 465–485.Google Scholar
Hoffmann, EK, Lambert, IH and Pedersen, SF (2009) Physiology of cell volume regulation in vertebrates. Physiol Rev 89, 193–277.Google Scholar
Humphreys, BD, Jiang, L, Chernova, MN and Alper, SL (1995) Hypertonic activation of AE2 anion exchanger in Xenopus oocytes via NHE-mediated intracellular alkalinization. Am J Physiol 268, C201–c209.Google Scholar
Jiang, L, Chernova, MN and Alper, SL (1997) Secondary regulatory volume increase conferred on Xenopus oocytes by expression of AE2 anion exchanger. Am J Physiol 272, C191–202.Google Scholar
Karaman, MW, Herrgard, S, Treiber, DK, Gallant, P, Atteridge, CE, Campbell, BT, Chan, KW, Ciceri, P, Davis, MI, Edeen, PT, Faraoni, R, Floyd, M, Hunt, JP, Lockhart, DJ, Milanov, ZV, Morrison, MJ, Pallares, G, Patel, HK, Pritchard, S, Wodicka, LM and Zarrinkar, PP (2008) A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol 26, 127–132.Google Scholar
Krump, E, Nikitas, K and Grinstein, S (1997) Induction of tyrosine phosphorylation and Na+/H+ exchanger activation during shrinkage of human neutrophils. J Biol Chem 272, 17303–17311.Google Scholar
Lawitts, JA and Biggers, JD (1992) Joint effects of sodium chloride, glutamine, and glucose in mouse preimplantation embryo culture media. Mol Reprod Dev 31, 189–194.Google Scholar
Lawitts, JA and Biggers, JD (1993) Culture of preimplantation embryos. Methods Enzymol 225, 153–164.Google Scholar
Lunn, JA and Rozengurt, E (2004) Hyperosmotic stress induces rapid focal adhesion kinase phosphorylation at tyrosines 397 and 577: role of Src family kinases and Rho family GTPases. J Biol Chem 279, 45266–45278.Google Scholar
Lunn, JA, Jacamo, R and Rozengurt, E (2007) Preferential phosphorylation of focal adhesion kinase tyrosine 861 is critical for mediating an anti-apoptotic response to hyperosmotic stress. J Biol Chem 282, 10370–10379.Google Scholar
Malo, ME and Fliegel, L (2006) Physiological role and regulation of the Na+/H+ exchanger. Can J Physiol Pharmacol 84, 1081–1095.Google Scholar
McGinnis, LK and Kinsey, WH (2015) Role of focal adhesion kinase in oocyte–follicle communication. Mol Reprod Dev 82, 90–102.Google Scholar
McGinnis, LK, Carroll, DJ and Kinsey, WH (2011) Protein tyrosine kinase signaling during oocyte maturation and fertilization. Mol Reprod Dev 78, 831–845.Google Scholar
McGinnis, LK, Luo, J and Kinsey, WH (2013) Protein tyrosine kinase signaling in the mouse oocyte cortex during sperm–egg interactions and anaphase resumption. Mol Reprod Dev 80, 260–272.Google Scholar
Rasmussen, LJ, Muller, HS, Jorgensen, B, Pedersen, SF and Hoffmann, EK (2015) Osmotic shrinkage elicits FAK- and Src phosphorylation and Src-dependent NKCC1 activation in NIH3T3 cells. Am J Physiol Cell Physiol 308, C101–c110.Google Scholar
Roberts, WG, Ung, E, Whalen, P, Cooper, B, Hulford, C, Autry, C, Richter, D, Emerson, E, Lin, J, Kath, J, Coleman, K, Yao, L, Martinez-Alsina, L, Lorenzen, M, Berliner, M, Luzzio, M, Patel, N, Schmitt, E, LaGreca, S, Jani, J, Wessel, M, Marr, E, Griffor, M and Vajdos, F (2008) Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271. Cancer Res 68, 1935–1944.Google Scholar
Romero, MF, Chen, AP, Parker, MD and Boron, WF (2013) The SLC4 family of bicarbonate (HCO3 –) transporters. Mol Aspects Med 34, 159–182.Google Scholar
Sardet, C, Counillon, L, Franchi, A and Pouyssegur, J (1990) Growth factors induce phosphorylation of the Na+/H+ antiporter, glycoprotein of 110 kD. Science 247, 723–726.Google Scholar
Schaller, MD, Hildebr, JD, Shannon, JD, Fox, JW, Vines, RR and Parsons, JT (1994) Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src. Mol Cell Biol 14, 1680–1688.Google Scholar
Schlaepfer, DD and Hunter, T (1996) Evidence for in vivo phosphorylation of the Grb2 SH2-domain binding site on focal adhesion kinase by Src-family protein-tyrosine kinases. Mol Cell Biol 16, 5623–5633.Google Scholar
Schlaepfer, DD, Mitra, SK and Ilic, D (2004) Control of motile and invasive cell phenotypes by focal adhesion kinase. Biochim Biophys Acta Mol Cell Biol Lipids 1692, 77–102.Google Scholar
Siyanov, V and Baltz, JM (2013) NHE1 is the sodium–hydrogen exchanger active in acute intracellular pH regulation in preimplantation mouse embryos. Biol Reprod 88, 157.Google Scholar
Steeves, CL, Lane, M, Bavister, BD, Phillips, KP and Baltz, JM (2001) Differences in intracellular pH regulation by Na+/H+ antiporter among 2-cell mouse embryos derived from females of different strains. Biol Reprod 65, 14–22.Google Scholar
Thomas, JA, Buchsbaum, RN, Zimniak, A and Racker, E (1979) Intracellular pH measurements in Ehrlich ascites tumor cells utilizing spectroscopic probes generated in situ. Biochemistry 18, 2210–2218.Google Scholar
Wendt, MK and Schiemann, WP (2009) Therapeutic targeting of the focal adhesion complex prevents oncogenic TGF-β signaling and metastasis. Breast Cancer Res 11, R68.Google Scholar
Wiemer, AJ, Wernimont, SA, Cung, T.-D, Bennin, DA, Beggs, HE and Huttenlocher, A (2013) The focal adhesion kinase inhibitor PF-562,271 impairs primary CD4+ cell activation. Biochem Pharmacol 86, 770–781.Google Scholar
Xu, B, Zhou, C, Meredith, M and Baltz, JM (2017) Acute cell volume regulation by Janus kinase 2-mediated sodium/hydrogen exchange activation develops at the late one-cell stage in mouse preimplantation embryos. Biol Reprod 96, 542–550.Google Scholar
Yoon, H, Choi, Y.-L, Song, J.-Y, Do, I, Kang, SY, Ko, Y.-H, Song, S and Kim, B.-G (2014) Targeted inhibition of FAK, PYK2 and BCL-XL synergistically enhances apoptosis in ovarian clear cell carcinoma cell lines. PLoS One 9, e88587.Google Scholar
Zhou, C and Baltz, JM (2013) JAK2 mediates the acute response to decreased cell volume in mouse preimplantation embryos by activating NHE1. J Cell Physiol 228, 428–438.Google Scholar
Zhou, C, FitzHarris, G, Alper, SL and Baltz, JM (2013) Na+/H+ exchange is inactivated during mouse oocyte meiosis, facilitating glycine accumulation that maintains embryo cell volume. J Cell Physiol 228, 2042–2053.Google Scholar