Back
 JBM  Vol.5 No.2 , February 2017
Role of Signal-Regulated Changes in Microtubule Stability Dynamics through α-Tubulin Phosphorylation on Ser/Tyr in Modulation of Salivary Gland Matrix Metalloproteinase-9 (MMP-9) Secretion in Response to Porphyromonas gingivalis and Ghrelin
Abstract: Up-regulation in salivary gland acinar cell MMP-9 secretion in response to proinflammatory challenge by periodontopathic bacterium, P. gingivalis relays heavily on the factors that influence the protein processing at the level of endoplasmic reticulum-to-Golgi trafficking, and occurs in concert with the changes in the stability dynamics of the major cytoskeleton polymeric structures, microtubules (MTs). In this study, we report that P. gingivalis LPS-elicited induction in the acinar cell MMP-9 secretion is accompanied by the enhancement in MT stabilization, while the modulatory influence of peptide hormone, ghrelin, is associated with MT destabilization. Further, we reveal that the changes in MT dynamics induced by the LPS and ghrelin occur through signal-regulated α-tubulin phosphorylation on Ser/Tyr. The LPS effect is reflected in a marked increase in PKCδ-mediated α-tubulin phosphorylation on Ser, whereas the modulatory influence of ghrelin on MT dynamics is manifested in by SFK-dependent phosphorylation of α-tubulin on Tyr. Moreover, we show that that the changes in MT dynamics, conferred by the LPS and ghrelin, affect the Golgi localization of GTP-Arf1 and the recruitment and activation of PKD2. The findings underscore the role of signal-regulated changes in MT stability dynamics through PKCδ/SFK-mediated α-tubulin phosphorylation on Ser/Tyr in controlling the salivary gland acinar cell MMP-9 secretion in response to P. gingivalis LPS as well as its modulation by ghrelin.
Cite this paper: Slomiany, B. and Slomiany, A. (2017) Role of Signal-Regulated Changes in Microtubule Stability Dynamics through α-Tubulin Phosphorylation on Ser/Tyr in Modulation of Salivary Gland Matrix Metalloproteinase-9 (MMP-9) Secretion in Response to Porphyromonas gingivalis and Ghrelin. Journal of Biosciences and Medicines, 5, 22-38. doi: 10.4236/jbm.2017.52003.
References

[1]   Colombo, A.P., Boches, S.K. and Cotton, S.L. (2009) Comparisons of Subgingival Microbial Profiles of Refractory Periodontitis, Severe Periodontitis, and Periodontal Health Using the Human Oral Microbe Identification Microarray. Journal of Periodontology, 80, 1421-1432.
https://doi.org/10.1902/jop.2009.090185

[2]   Slomiany, B.L. and Slomiany, A. (2010) Suppression by Ghrelin of Porphyromonas gingivalis-Induced Constitutive Nitric Oxide Synthase S-Nitrosylation and Apoptosis in Salivary Gland Acinar Cells. Journal of Signal Transduction, 2010, Article ID: 643642.
https://doi.org/10.1155/2010/643642

[3]   Mysak, J., Podzimek, S., Sommerova, P., et al. (2014) Porphyromonas gingivalis: Major Periodontopathic Pathogen Overview. Journal of Immunology Research, 2014, Article ID: 476068.
https://doi.org/10.1155/2014/476068

[4]   Slomiany, B.L. and Slomiany, A. (2011) Ghrelin-Induced cSrc Activation through Constitutive Nitric Oxide Synthase-Dependent S-Nitrosylation in Modulation of Salivary Gland Acinar Cell Inflammatory Responses to Porphyromonas gingivalis. American Journal of Molecular Biology, 2, 43-51.
https://doi.org/10.4236/ajmb.2011.12006

[5]   Slomiany, B.L. and Slomiany, A. (2015) Porphyromonas gingivalis-Stimulated TACE Activationfor TGF-α Ectodomian Shedding and EGFR Transactivation in Salivary Gland Cells Requires Rac1-Dependent p38 MAPK Membrane Localization. Journal of Biosciences and Medicines, 3, 42-53.
https://doi.org/10.4236/jbm.2015.311005

[6]   Ejeil, A.L., Igondio-Tchen, S., Ghomrasseni, S., Pellat, B., Godeau, G. and Gogly, B. (2003) Expression of Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinases (TIMPs) in Healthy and Diseased Human Gingiva. Journal of Periodontology, 74, 188-195.
https://doi.org/10.1902/jop.2003.74.2.188

[7]   Vandooren, J., Van den Steen, P.E. and Opdenakker, G. (2013) Biochemistry and Molecular Biology of Gelatinase B or Matrix Metalloproteinase-9 (MMP-9): The Next Decade. Critical Reviews in Biochemistry and Molecular Biology, 48, 222-272.
https://doi.org/10.3109/10409238.2013.770819

[8]   Slomiany, B.L. and Slomiany, A. (2016) Role of Rac1/p38 and ERK-Dependent Cytosolic Phospholipase A2 Activation in Porphyromonas gingivalis-Evoked Induction in Matrix Metalloproteinase-9 (MMP-9) Release by Salivary Gland Cells. Journal of Biosciences and Medicines, 4, 68-79.
https://doi.org/10.4236/jbm.2016.44010

[9]   Donaldson, J.G. and Jackson, C.L. (2011) ARF Family G Proteins and Their Regulators: Roles in Membrane Transport, Development and Disease. Nature Reviews Molecular Cell Biology, 12, 362-375.
https://doi.org/10.1038/nrm3117

[10]   Rozengurt, E. (2011) Protein Kinase D Signaling: Multiple Biological Functions in Health and Disease. Physiology, 26, 23-33.
https://doi.org/10.1152/physiol.00037.2010

[11]   Bonnemaison, M.L., Eipper, B.A. and Mains, R.E. (2013) Role of Adaptor Proteins in Secretory Granule Biogenesis and Maturation. Frontiers in Endocrinology, 4, 101.
https://doi.org/10.3389/fendo.2013.00101

[12]   Bourgoin, S.G. and El Azreq, M.A. (2012) Small Inhibitors of ADP-Ribosylation Factor Activation and Function in Mammalian Cells. World Journal of Pharmacology, 1, 55-64.
https://doi.org/10.5497/wjp.v1.i4.55

[13]   Cherfils, J. and Zeghouf, M. (2013) Regulation of Small GTPases by GEFs, GAPs, and GDIs. Physiological Reviews, 93, 269-309.
https://doi.org/10.1152/physrev.00003.2012

[14]   Eiseler, T., Wille, C., Koehler, C., Illing, A. and Seufferlein, T. (2016) Protein Kinase D2 Assembles a Multiprotein Complex at the Trans-Golgi Network to Regulate Matrix Metalloproteinase Secretion. Journal of Biological Chemistry, 291, 462-477.
https://doi.org/10.1074/jbc.M115.673582

[15]   Slomiany, B.L. and Slomiany, A. (2016) Role of Protein Kinase D2 Phosphorylation on Tyr in Modulation by Ghrelin of Helicobacter pylori-Induced Up-Regulation in Gastric Mucosal Matrix Metalloproteinase-9 (MMP-9) Secretion. Inflammopharmacology, 24, 119-126.
https://doi.org/10.1007/s10787-016-0267-2

[16]   Goode, B.L., Drubin, D.G. and Barnes, G. (2000) Functional Cooperation between the Microtubule and Actin in Cytoskeletons. Current Opinions in Cell Biology, 12, 63-71.
https://doi.org/10.1016/S0955-0674(99)00058-7

[17]   Hanania, R., Sun, H.S., Xu, K., et al. (2012) Classically Activated Macrophages Use Stable Microtubules for Matrix Metalloproteinase-9 (MMP-9) Secretion. Journal of Biological Chemistry, 287, 8468-8483.
https://doi.org/10.1074/jbc.M111.290676

[18]   Gu, S., Liu, Y., Zhu, B., et al. (2016) Loss of α-Tubulin Acetylation is Associated with TGF-β-induced Epithelial-Mesenchymal Transition. Journal of Biological Chemistry, 291, 5396-5405.
https://doi.org/10.1074/jbc.M115.713123

[19]   Howes, S.C., Alushin, G.M., Shida, T., Nachury, M.V. and Nogales, E. (2014) Effects of Tubulin Acetylation and Tubulin Acetyltransferase Binding on Microtubule Structure. Molecular Biology of the Cell, 25, 257-266.
https://doi.org/10.1091/mbc.E13-07-0387

[20]   Nirschl, J.J., Magiera, M.M., Lazarus, J.E., Janke, C. and Holzbaur, E.L.F. (2016) α-Tubulin Tyrosination and CLIP-170 Phosphorylation Regulate the Initiation of Dynein-Driven Transport in Neurons. Cell Reports, 14, 2637-2652.
https://doi.org/10.1016/j.celrep.2016.02.046

[21]   Jordan, M.A. and Wilson, L. (2004) Microtubules as a Target for Anticancer Drugs. Nature Reviews, 4, 253-265.
https://doi.org/10.1038/nrc1317

[22]   Fourest-Lieuvin, A., Peris, L., Gache, V., et al. (2006) Microtubule Regulation in Mitosis: Tubulin Phosphorylation by the Cyclin-dependent Kinase Cdk1. Molecular Biology of the Cell, 17, 1041-1050.
https://doi.org/10.1091/mbc.E05-07-0621

[23]   Slomiany, B.L. and Slomiany, A. (2016) Role of α-Tubulin Acetylation and Protein Kinase D2 Ser/Tyr Phosphorylation in Modulation by Ghrelin of Porphyromonas gingivalis-induced Enhancement in MMP-9 Secretion by Salivary Gland Cells. Journal of Biosciences and Medicines, 4, 82-94.
https://doi.org/10.4236/jbm.2016.47009

[24]   Laurent, C.E., Delfino, F.J., Cheng, H.Y. and Smithgall, T.E. (2004) The Human c-Fes Tyrosine Kinase Binds Tubulin and Microtubules Through Separate Domains and Promotes Microtubule Assembly. Molecular Cell Biology, 24, 9351-9358.
https://doi.org/10.1128/MCB.24.21.9351-9358.2004

[25]   Ma, X. and Sayeski, P.P. (2007) Identification of Tubulin as a Substrate of Jak2 Tyrosine Kinase and Its Role in Jak2-Dependent Signaling. Biochemistry, 46, 7153-7162.
https://doi.org/10.1021/bi700101n

[26]   De, S., Tsimounis, A., Chen, X. and Rotenberg, S.A. (2014) Phosphorylation of α-Tubulin by Protein Kinase C Stimulates Microtubule Dynamics in Human Breast Cells. Cytoskeleton, 71, 252-272.
https://doi.org/10.1002/cm.21167

[27]   Yu, Y., Gaillard, S., Phillip, J.M., et al. (2015) Inhibition of Spleen Tyrosine Kinase Potentiates Paclitaxel-induced Cytotoxicity in Ovarian Cancer Cells by Stabilizing Microtubules. Cancer Cell, 28, 82-96.
https://doi.org/10.1016/j.ccell.2015.05.009

[28]   Slomiany, B.L. and Slomiany, A. (2015) Porphyromonas gingivalis-Induced GEF Dock180 Activation by Src/PKCδ-Dependent Phosphorylation Mediates PLCγ2 Amplification in Salivary Gland Acinar Cells: Effect of Ghrelin. Journal of Biosciences and Medicines, 3, 66-77.
https://doi.org/10.4236/jbm.2015.37008

[29]   Slomiany, A., Grabska, M., Slomiany, B.A., et al. (1993) Intracellular Transport, Organelle Biogenesis and Establishment of Golgi Identity: Impact of Brefeldin A on the Activity of Lipid Synthesizing Enzymes. International Journal of Biochemistry, 25, 891-901.
https://doi.org/10.1016/0020-711X(93)90245-A

[30]   Slomiany, B.L. and Slomiany, A. (2016) Helicobacter pylori-Induced Changes in Microtubule Dynamics Conferred by α-Tubulin Phosphorylation on Ser/Tyr Mediate Gastric Mucosal Secretion of Matrix Metalloproteinase-9 (MMP-9) and Its Modulation by Ghrelin. Inflammopharmacology, 24, 197-205.
https://doi.org/10.1007/s10787-016-0278-z

[31]   Visa, N.E., De Lemos-Chiarandini, C., Gravotta, D., Sabatini, D.D. and Kreibich, G. (1995) The Brefeldin A-Induced Retrograde Transport from the Golgi Apparatus to the Endoplasmic Reticulum Depends on Calcium Sequestered to Intracellular Stores. Journal of Biological Chemistry, 270, 25960-25967.
https://doi.org/10.1074/jbc.270.43.25960

 
 
Top