Thrombin receptor activation causes rapid neural cell rounding and neurite retraction independent of classic second messengers

doi:10.1083/jcb.118.2.411

This Article

	Full Text (PDF, 1765K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Jalink, K.
	Articles by Moolenaar, W. H.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Jalink, K.
	Articles by Moolenaar, W. H.


Social Bookmarking

	What's this?

ARTICLES

Thrombin receptor activation causes rapid neural cell rounding and neurite retraction independent of classic second messengers

K Jalink and WH Moolenaar
Division of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam.

The protease thrombin is a potent activator of various cell types. Thrombin cleaves and thereby activates its own seven-transmembrane- domain receptor which couples to G proteins. Thrombin also can inhibit neuronal differentiation, supposedly by degrading components of the extracellular matrix. Here we report that active thrombin induces immediate cell rounding and neurite retraction in differentiating N1E- 115 and NG108-15 neural cells in serum-free culture. Serum (0.5-5% vol/vol) evokes similar responses, but the cell-rounding and neurite- retracting activity of serum is not attributable to thrombin. Neural cell rounding is transient, subsiding after 10-15 min, and subject to homologous desensitization, whereas retracted neurites rapidly degenerate. Thrombin action is inhibited by cytochalasin, but not colchicine. A novel 14-amino acid peptide agonist of the thrombin receptor fully mimics thrombin's morphoregulatory activity, indicating that thrombin-induced shape changes are receptor-mediated and not secondary to extracellular matrix degradation. Although thrombin receptors couple to phosphoinositide hydrolysis and Ca2+ mobilization, thrombin-induced shape changes appear to depend neither on the Ca2+/protein kinase C- nor the cyclic nucleotide-mediated signal transduction pathways; however, the morphological response to thrombin is blocked by pervanadate, an inhibitor of tyrosine phosphatases, and by broad-specificity kinase inhibitors. Our results suggest that the thrombin receptor communicates to an as-yet-uncharacterized effector to reorganize the actin cytoskeleton and to reverse the differentiated phenotype of neural cells.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Fujita, T., Liu, T., Nakatsuka, T., Kumamoto, E. (2009). Proteinase-Activated Receptor-1 Activation Presynaptically Enhances Spontaneous Glutamatergic Excitatory Transmission in Adult Rat Substantia Gelatinosa Neurons. J. Neurophysiol. 102: 312-319 [Abstract] [Full Text]
Davies, S. L., Gibbons, C. E., Vizard, T., Ward, D. T. (2006). Ca2+-sensing receptor induces Rho kinase-mediated actin stress fiber assembly and altered cell morphology, but not in response to aromatic amino acids. Am. J. Physiol. Cell Physiol. 290: C1543-C1551 [Abstract] [Full Text]
Peterson, Y. K., Kelly, P., Weinbaum, C. A., Casey, P. J. (2006). A Novel Protein Geranylgeranyltransferase-I Inhibitor with High Potency, Selectivity, and Cellular Activity. J. Biol. Chem. 281: 12445-12450 [Abstract] [Full Text]
Rohatgi, T., Sedehizade, F., Reymann, K. G., Reiser, G. (2004). Protease-Activated Receptors in Neuronal Development, Neurodegeneration, and Neuroprotection: Thrombin as Signaling Molecule in the Brain. Neuroscientist 10: 501-512 [Abstract]
Wylie, S. R., Chantler, P. D. (2003). Myosin IIA Drives Neurite Retraction. Mol. Biol. Cell 14: 4654-4666 [Abstract] [Full Text]
Price, L. S., Langeslag, M., Klooster, J. P. t., Hordijk, P. L., Jalink, K., Collard, J. G. (2003). Calcium Signaling Regulates Translocation and Activation of Rac. J. Biol. Chem. 278: 39413-39421 [Abstract] [Full Text]
Fournier, A. E., Takizawa, B. T., Strittmatter, S. M. (2003). Rho Kinase Inhibition Enhances Axonal Regeneration in the Injured CNS. J. Neurosci. 23: 1416-1423 [Abstract] [Full Text]
Contos, J. J. A., Ishii, I., Chun, J. (2001). Lysophosphatidic Acid Receptors. Mol. Pharmacol. 58: 1188-1196 [Abstract] [Full Text]
Mahajan, V. B., Pai, K. S., Lau, A., Cunningham, D. D. (2000). Creatine kinase, an ATP-generating enzyme, is required for thrombin receptor signaling to the cytoskeleton. Proc. Natl. Acad. Sci. USA 97: 12062-12067 [Abstract] [Full Text]
Wahl, S., Barth, H., Ciossek, T., Aktories, K., Mueller, B. K. (2000). Ephrin-A5 Induces Collapse of Growth Cones by Activating Rho and Rho Kinase. JCB 149: 263-270 [Abstract] [Full Text]
Pindon, A., Berry, M., Hantai, D. (2000). Thrombomodulin as a New Marker of Lesion-Induced Astrogliosis: Involvement of Thrombin through the G-Protein-Coupled Protease-Activated Receptor-1. J. Neurosci. 20: 2543-2550 [Abstract] [Full Text]
Carhuapoma, J. R., Wang, P. Y., Beauchamp, N. J., Keyl, P. M., Hanley, D. F., Barker, P. B. (2000). Diffusion-Weighted MRI and Proton MR Spectroscopic Imaging in the Study of Secondary Neuronal Injury After Intracerebral Hemorrhage. Stroke 31: 726-732 [Abstract] [Full Text]
Ross, S., Essary, B., de la Houssaye, B. A., Pan, Z., Mikule, K., Mubarak, O., Pfenninger, K. H. (2000). Thrombin Causes Pseudopod Detachment via a Pathway Involving Cytosolic Phospholipase A2 and 12/15- Lipoxygenase Products. Cell Growth Differ. 11: 19-30 [Abstract] [Full Text]
de la Houssaye, B. A., Mikule, K., Nikolic, D., Pfenninger, K. H. (1999). Thrombin-Induced Growth Cone Collapse: Involvement of Phospholipase A2 and Eicosanoid Generation. J. Neurosci. 19: 10843-10855 [Abstract] [Full Text]
Behar, O., Mizuno, K., Badminton, M., Woolf, C. J. (1999). Semaphorin 3A growth cone collapse requires a sequence homologous to tarantula hanatoxin. Proc. Natl. Acad. Sci. USA 96: 13501-13505 [Abstract] [Full Text]
Majumdar, M., Seasholtz, T. M., Buckmaster, C., Toksoz, D., Brown, J. H. (1999). A Rho Exchange Factor Mediates Thrombin and Galpha 12-induced Cytoskeletal Responses. J. Biol. Chem. 274: 26815-26821 [Abstract] [Full Text]
Nguyen, B., Carbajal, M. E., Vitale, M. L. (1999). Intracellular Mechanisms Involved in Dopamine-Induced Actin Cytoskeleton Organization and Maintenance of a Round Phenotype in Cultured Rat Lactotrope Cells. Endocrinology 140: 3467-3477 [Abstract] [Full Text]
Seasholtz, T. M., Majumdar, M., Brown, J. H. (1999). MINIREVIEW: Rho as a Mediator of G Protein-Coupled Receptor Signaling. Mol. Pharmacol. 55: 949-956 [Full Text]
Kranenburg, O., Poland, M., van Horck, F. P.�G., Drechsel, D., Hall, A., Moolenaar, W. H. (1999). Activation of RhoA by Lysophosphatidic Acid and Galpha 12/13 Subunits in Neuronal Cells: Induction of Neurite Retraction. Mol. Biol. Cell 10: 1851-1857 [Abstract] [Full Text]
Seasholtz, T. M., Majumdar, M., Kaplan, D. D., Brown, J. H. (1999). Rho and Rho Kinase Mediate Thrombin-Stimulated Vascular Smooth Muscle Cell DNA Synthesis and Migration. Circ. Res. 84: 1186-1193 [Abstract] [Full Text]
Nakamura, T., Takeuchi, K., Muraoka, S., Takezoe, H., Takahashi, N., Mori, N. (1999). A Neurally Enriched Coronin-like Protein, ClipinC, Is a Novel Candidate for an Actin Cytoskeleton-Cortical Membrane-linking Protein. J. Biol. Chem. 274: 13322-13327 [Abstract] [Full Text]
Katoh, H., Aoki, J., Yamaguchi, Y., Kitano, Y., Ichikawa, A., Negishi, M. (1998). Constitutively Active Galpha 12, Galpha 13, and Galpha q Induce Rho-dependent Neurite Retraction through Different Signaling Pathways. J. Biol. Chem. 273: 28700-28707 [Abstract] [Full Text]
Wylie, S. R., Wu, P.-j., Patel, H., Chantler, P. D. (1998). A conventional myosin motor drives neurite outgrowth. Proc. Natl. Acad. Sci. USA 95: 12967-12972 [Abstract] [Full Text]
Turgeon, V. L., Lloyd, E. D., Wang, S., Festoff, B. W., Houenou, L. J. (1998). Thrombin Perturbs Neurite Outgrowth and Induces Apoptotic Cell Death in Enriched Chick Spinal Motoneuron Cultures through Caspase Activation. J. Neurosci. 18: 6882-6891 [Abstract] [Full Text]
Dong, J.-M., Leung, T., Manser, E., Lim, L. (1998). cAMP-induced Morphological Changes Are Counteracted by the Activated RhoA Small GTPase and the Rho Kinase ROKalpha. J. Biol. Chem. 273: 22554-22562 [Abstract] [Full Text]
Wang, Q., Zheng, J. Q. (1998). cAMP-Mediated Regulation of Neurotrophin-Induced Collapse of Nerve Growth Cones. J. Neurosci. 18: 4973-4984 [Abstract] [Full Text]
Hirose, M., Ishizaki, T., Watanabe, N., Uehata, M., Kranenburg, O., Moolenaar, W. H., Matsumura, F., Maekawa, M., Bito, H., Narumiya, S. (1998). Molecular Dissection of the Rho-associated Protein Kinase (p160ROCK)-regulated Neurite Remodeling in Neuroblastoma N1E-115 Cells. JCB 141: 1625-1636 [Abstract] [Full Text]
Kim, S., Nelson, P. G. (1998). Transcriptional Regulation of the Prothrombin Gene in Muscle. J. Biol. Chem. 273: 11923-11929 [Abstract] [Full Text]
Altun-Gultekin, Z. F., Chandriani, S., Bougeret, C., Ishizaki, T., Narumiya, S., de Graaf, P., Van Bergen en Henegouwen, P., Hanafusa, H., Wagner, J. A., Birge, R. B. (1998). Activation of Rho-Dependent Cell Spreading and Focal Adhesion Biogenesis by the v-Crk Adaptor Protein. Mol. Cell. Biol. 18: 3044-3058 [Abstract] [Full Text]
Shimizu, C., Yoshida, S., Shibata, M., Kato, K., Momota, Y., Matsumoto, K., Shiosaka, T., Midorikawa, R., Kamachi, T., Kawabe, A., Shiosaka, S. (1998). Characterization of Recombinant and Brain Neuropsin, a Plasticity-related Serine Protease. J. Biol. Chem. 273: 11189-11196 [Abstract] [Full Text]
Majumdar, M., Seasholtz, T. M., Goldstein, D., de Lanerolle, P., Brown, J. H. (1998). Requirement for Rho-mediated Myosin Light Chain Phosphorylation in Thrombin-stimulated Cell Rounding and Its Dissociation from Mitogenesis. J. Biol. Chem. 273: 10099-10106 [Abstract] [Full Text]
Postma, F. R., Hengeveld, T., Alblas, J., Giepmans, B. N.G., Zondag, G. C.M., Jalink, K., Moolenaar, W. H. (1998). Acute loss of Cell-Cell Communication Caused by G Protein-coupled Receptors: A Critical Role for c-Src. JCB 140: 1199-1209 [Abstract] [Full Text]
Katoh, H., Aoki, J., Ichikawa, A., Negishi, M. (1998). p160 RhoA-binding Kinase ROKalpha Induces Neurite Retraction. J. Biol. Chem. 273: 2489-2492 [Abstract] [Full Text]
Belkin, A. M., Retta, S. F., Pletjushkina, O. Y., Balzac, F., Silengo, L., Fassler, R., Koteliansky, V. E., Burridge, K., Tarone, G. (1997). Muscle {beta}1D Integrin Reinforces the Cytoskeleton-Matrix Link: Modulation of Integrin Adhesive Function by Alternative Splicing. JCB 139: 1583-1595 [Abstract] [Full Text]
Leeuwen, F. N. v., Kain, H. E.T., Kammen, R. A. v. d., Michiels, F., Kranenburg, O. W., Collard, J. G. (1997). The Guanine Nucleotide Exchange Factor Tiam1 Affects Neuronal Morphology; Opposing Roles for the Small GTPases Rac and Rho. JCB 139: 797-807 [Abstract] [Full Text]
Jin, Z., Strittmatter, S. M. (1997). Rac1 Mediates Collapsin-1-Induced Growth Cone Collapse. J. Neurosci. 17: 6256-6263 [Abstract] [Full Text]
Gebbink, M. F.B.G., Kranenburg, O., Poland, M., Horck, F. P.G. v., Houssa, B., Moolenaar, W. H. (1997). Identification of a Novel, Putative Rho-specific GDP/GTP Exchange Factor and a RhoA-binding Protein: Control of Neuronal Morphology. JCB 137: 1603-1613 [Abstract] [Full Text]
Luthi, A., Putten, H. v. d., Botteri, F. M., Mansuy, I. M., Meins, M., Frey, U., Sansig, G., Portet, C., Schmutz, M., Schroder, M., Nitsch, C., Laurent, J.-P., Monard, D. (1997). Endogenous Serine Protease Inhibitor Modulates Epileptic Activity and Hippocampal Long-Term Potentiation. J. Neurosci. 17: 4688-4699 [Abstract] [Full Text]
Kranenburg, O, Poland, M, Gebbink, M, Oomen, L, Moolenaar, W. (1997). Dissociation of LPA-induced cytoskeletal contraction from stress fiber formation by differential localization of RhoA. J. Cell Sci. 110: 2417-2427 [Abstract]
Suidan, H. S., Niclou, S. P., Dreessen, J., Beltraminelli, N., Monard, D. (1996). The Thrombin Receptor Is Present in Myoblasts and Its Expression Is Repressed upon Fusion. J. Biol. Chem. 271: 29162-29169 [Abstract] [Full Text]
Mandell, J. W., Banker, G. A. (1996). A Spatial Gradient of Tau Protein Phosphorylation in Nascent Axons. J. Neurosci. 16: 5727-5740 [Abstract] [Full Text]
Watanabe, E., Maeda, N., Matsui, F., Kushima, Y., Noda, M., Oohira, A. (1995). Neuroglycan C, a Novel Membrane-spanning Chondroitin Sulfate Proteoglycan That Is Restricted to the Brain. J. Biol. Chem. 270: 26876-26882 [Abstract] [Full Text]
Negrescu, E. V., de Quintana, K. L., Siess, W. (1995). Platelet Shape Change Induced by Thrombin Receptor Activation. J. Biol. Chem. 270: 1057-1061 [Abstract] [Full Text]
Murugasu-Oei, B, Rodrigues, V, Yang, X, Chia, W (1995). Masquerade: a novel secreted serine protease-like molecule is required for somatic muscle attachment in the Drosophila embryo.. Genes Dev. 9: 139-154 [Abstract]
Mansuy, I. M., van der Putten, H., Schmid, P., Meins, M., Botteri, F. M., Monard, D. (1993). Variable and multiple expression of Protease Nexin-1 during mouse organogenesis and nervous system development. Development 119: 1119-1134 [Abstract]
Moolenaar, W.H., van der Bend, R.L., van Corven, E.J., Jalink, K., Eichholtz, T., van Blitterswijk, W.J. (1992). Lysophosphatidic Acid: A Novel Phospholipid with Hormone- and Growth Factor-like Activities. Cold Spring Harb Symp Quant Biol 57: 163-167 [Abstract]
Togashi, H., Nagata, K.-i., Takagishi, M., Saitoh, N., Inagaki, M. (2000). Functions of a Rho-specific Guanine Nucleotide Exchange Factor in Neurite Retraction. POSSIBLE ROLE OF A PROLINE-RICH MOTIF OF KIAA0380 IN LOCALIZATION. J. Biol. Chem. 275: 29570-29578 [Abstract] [Full Text]
van der Wal, J., Habets, R., Varnai, P., Balla, T., Jalink, K. (2001). Monitoring Agonist-induced Phospholipase C Activation in Live Cells by Fluorescence Resonance Energy Transfer. J. Biol. Chem. 276: 15337-15344 [Abstract] [Full Text]
Sagi, S. A., Seasholtz, T. M., Kobiashvili, M., Wilson, B. A., Toksoz, D., Brown, J. H. (2001). Physical and Functional Interactions of Galpha q with Rho and Its Exchange Factors. J. Biol. Chem. 276: 15445-15452 [Abstract] [Full Text]
Pai, K. S., Mahajan, V. B., Lau, A., Cunningham, D. D. (2001). Thrombin Receptor Signaling to Cytoskeleton Requires Hsp90. J. Biol. Chem. 276: 32642-32647 [Abstract] [Full Text]