Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

J. Cell Biol. 147 (4): 707-714

Copyright © 1999 by the Rockefeller University Press.


Original Article

Protein Tyrosine Phosphatase {alpha} (Ptp{alpha}) and Contactin Form a Novel Neuronal Receptor Complex Linked to the Intracellular Tyrosine Kinase Fyn

Li Zenga, Luca D'Alessandrib, Markus B. Kalouseka, Lloyd Vaughanb, , and Catherine J. Pallena

a Institute for Molecular and Cell Biology, Singapore 117609, Republic of Singapore
b Institute for Biochemistry, ETH-Zurich, CH-8092 Zurich, Switzerland
Institute for Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Republic of Singapore.65-779-111765-874-3742

Abstract: Glycosyl phosphatidylinositol (GPI)–linked receptors and receptor protein tyrosine phosphatases (RPTPs), both play key roles in nervous system development, although the molecular mechanisms are largely unknown. Despite lacking a transmembrane domain, GPI receptors can recruit intracellular src family tyrosine kinases to receptor complexes. Few ligands for the extracellular regions of RPTPs are known, relegating most to the status of orphan receptors. We demonstrate that PTP{alpha}, an RPTP that dephosphorylates and activates src family kinases, forms a novel membrane-spanning complex with the neuronal GPI-anchored receptor contactin. PTP{alpha} and contactin associate in a lateral (cis) complex mediated through the extracellular region of PTP{alpha}. This complex is stable to isolation from brain lysates or transfected cells through immunoprecipitation and to antibody-induced coclustering of PTP{alpha} and contactin within cells. This is the first demonstration of a receptor PTP in a cis configuration with another cell surface receptor, suggesting an additional mode for regulation of a PTP. The transmembrane and catalytic nature of PTP{alpha} indicate that it likely forms the transducing element of the complex, and we postulate that the role of contactin is to assemble a phosphorylation-competent system at the cell surface, conferring a dynamic signal transduction capability to the recognition element.

Key Words: PTP{alpha} • tyrosine phosphatase • glycosyl phosphatidylinositol • neural signal transduction



L. Zeng, L. D'Alessandri, and M.B. Kalousek contributed equally to this work.

M.B. Kalousek's present address is Laves-Arzneimittel GmbH, CH-6247 Schötz, Switzerland.

Abbreviations used in this paper: FN-III, fibronectin type III; GPI, glycosyl phosphatidylinositol; PTP, protein tyrosine phosphatase; RPTP, receptor protein tyrosine phosphatase; VSVG, vaccinia stomatitis virus glycoprotein.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Contactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system.
G. Colakoglu, U. Bergstrom-Tyrberg, E. O. Berglund, and B. Ranscht (2014)
PNAS 111, E394-E403
   Abstract »    Full Text »    PDF »
Neural Cell Adhesion Molecule-Mediated Fyn Activation Promotes GABAergic Synapse Maturation in Postnatal Mouse Cortex.
B. Chattopadhyaya, E. Baho, Z. J. Huang, M. Schachner, and G. Di Cristo (2013)
J. Neurosci. 33, 5957-5968
   Abstract »    Full Text »    PDF »
PTP{alpha}-mediated Src activation by EGF in human breast cancer cells.
J. Wang, L. Yu, and X. Zheng (2013)
Acta Biochim Biophys Sin 45, 320-329
   Abstract »    Full Text »    PDF »
Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development.
G. R. Anderson, T. Galfin, W. Xu, J. Aoto, R. C. Malenka, and T. C. Sudhof (2012)
PNAS 109, 18120-18125
   Abstract »    Full Text »    PDF »
Loss of Protein-tyrosine Phosphatase {alpha} (PTP{alpha}) Increases Proliferation and Delays Maturation of Oligodendrocyte Progenitor Cells.
P.-S. Wang, J. Wang, Y. Zheng, and C. J. Pallen (2012)
J. Biol. Chem. 287, 12529-12540
   Abstract »    Full Text »    PDF »
A complex between contactin-1 and the protein tyrosine phosphatase PTPRZ controls the development of oligodendrocyte precursor cells.
S. Lamprianou, E. Chatzopoulou, J.-L. Thomas, S. Bouyain, and S. Harroch (2011)
PNAS 108, 17498-17503
   Abstract »    Full Text »    PDF »
Receptor-like Protein-tyrosine Phosphatase {alpha} Enhances Cell Surface Expression of Neural Adhesion Molecule NB-3.
H. Ye, T. Zhao, Y. L. J. Tan, J. Liu, C. J. Pallen, and Z.-C. Xiao (2011)
J. Biol. Chem. 286, 26071-26080
   Abstract »    Full Text »    PDF »
Protein-tyrosine Phosphatase {alpha} Acts as an Upstream Regulator of Fyn Signaling to Promote Oligodendrocyte Differentiation and Myelination.
P.-S. Wang, J. Wang, Z.-C. Xiao, and C. J. Pallen (2009)
J. Biol. Chem. 284, 33692-33702
   Abstract »    Full Text »    PDF »
Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn.
S.-H. Lim, S.-K. Kwon, M. K. Lee, J. Moon, D. G. Jeong, E. Park, S. J. Kim, B. C. Park, S. C. Lee, S.-E. Ryu, et al. (2009)
EMBO J. 28, 3564-3578
   Abstract »    Full Text »    PDF »
Protein tyrosine phosphatase-{alpha} complexes with the IGF-I receptor and undergoes IGF-I-stimulated tyrosine phosphorylation that mediates cell migration.
S. C. Chen, R. S. Khanna, D. C. Bessette, L. A. Samayawardhena, and C. J. Pallen (2009)
Am J Physiol Cell Physiol 297, C133-C139
   Abstract »    Full Text »    PDF »
Contactin-1 Is a Functional Receptor for Neuroregulatory Chondroitin Sulfate-E.
T. Mikami, D. Yasunaga, and H. Kitagawa (2009)
J. Biol. Chem. 284, 4494-4499
   Abstract »    Full Text »    PDF »
Protein-tyrosine Phosphatase {alpha} Regulates Stem Cell Factor-dependent c-Kit Activation and Migration of Mast Cells.
L. A. Samayawardhena and C. J. Pallen (2008)
J. Biol. Chem. 283, 29175-29185
   Abstract »    Full Text »    PDF »
Activation of oligodendroglial Fyn kinase enhances translation of mRNAs transported in hnRNP A2-dependent RNA granules.
R. White, C. Gonsior, E.-M. Kramer-Albers, N. Stohr, S. Huttelmaier, and J. Trotter (2008)
J. Cell Biol. 181, 579-586
   Abstract »    Full Text »    PDF »
Structural Requirement of TAG-1 for Retinal Ganglion Cell Axons and Myelin in the Mouse Optic Nerve.
E. Chatzopoulou, A. Miguez, M. Savvaki, G. Levasseur, A. Muzerelle, M.-P. Muriel, O. Goureau, K. Watanabe, L. Goutebroze, P. Gaspar, et al. (2008)
J. Neurosci. 28, 7624-7636
   Abstract »    Full Text »    PDF »
Voltage-Gated Na+ Channel {beta}1 Subunit-Mediated Neurite Outgrowth Requires Fyn Kinase and Contributes to Postnatal CNS Development In Vivo.
W. J. Brackenbury, T. H. Davis, C. Chen, E. A. Slat, M. J. Detrow, T. L. Dickendesher, B. Ranscht, and L. L. Isom (2008)
J. Neurosci. 28, 3246-3256
   Abstract »    Full Text »    PDF »
Neural recognition molecules CHL1 and NB-3 regulate apical dendrite orientation in the neocortex via PTP{alpha}.
H. Ye, Y. L. J. Tan, S. Ponniah, Y. Takeda, S.-Q. Wang, M. Schachner, K. Watanabe, C. J. Pallen, and Z.-C. Xiao (2008)
EMBO J. 27, 188-200
   Abstract »    Full Text »    PDF »
RPTP{alpha} is required for rigidity-dependent inhibition of extension and differentiation of hippocampal neurons.
A. Kostic, J. Sap, and M. P. Sheetz (2007)
J. Cell Sci. 120, 3895-3904
   Abstract »    Full Text »    PDF »
Tyrosine Phosphatases {varepsilon} and {alpha} Perform Specific and Overlapping Functions in Regulation of Voltage-gated Potassium Channels in Schwann Cells.
Z. Tiran, A. Peretz, T. Sines, V. Shinder, J. Sap, B. Attali, and A. Elson (2006)
Mol. Biol. Cell 17, 4330-4342
   Abstract »    Full Text »    PDF »
Regulation of Cell Adhesion by Protein-tyrosine Phosphatases: II. CELL-CELL ADHESION.
J. L. Sallee, E. S. Wittchen, and K. Burridge (2006)
J. Biol. Chem. 281, 16189-16192
   Abstract »    Full Text »    PDF »
Knockdown of contactin-1 expression suppresses invasion and metastasis of lung adenocarcinoma..
J.-L. Su, C.-Y. Yang, J.-Y. Shih, L.-H. Wei, C.-Y. Hsieh, Y.-M. Jeng, M.-Y. Wang, P.-C. Yang, and M.-L. Kuo (2006)
Cancer Res. 66, 2553-2561
   Abstract »    Full Text »    PDF »
Protein Tyrosine Phosphatase {alpha} Regulates Fyn Activity and Cbp/PAG Phosphorylation in Thymocyte Lipid Rafts.
L. Maksumova, H. T. Le, F. Muratkhodjaev, D. Davidson, A. Veillette, and C. J. Pallen (2005)
J. Immunol. 175, 7947-7956
   Abstract »    Full Text »    PDF »
Interaction of the Insulin Receptor with the Receptor-Like Protein Tyrosine Phosphatases PTP{alpha} and PTP{epsilon} in Living Cells.
D. Lacasa, N. Boute, and T. Issad (2005)
Mol. Pharmacol. 67, 1206-1213
   Abstract »    Full Text »    PDF »
Age-Dependent Enhancement of Hippocampal Long-Term Potentiation and Impairment of Spatial Learning through the Rho-Associated Kinase Pathway in Protein Tyrosine Phosphatase Receptor Type Z-Deficient Mice.
K. Niisato, A. Fujikawa, S. Komai, T. Shintani, E. Watanabe, G. Sakaguchi, G. Katsuura, T. Manabe, and M. Noda (2005)
J. Neurosci. 25, 1081-1088
   Abstract »    Full Text »    PDF »
RPTP{alpha} is essential for NCAM-mediated p59fyn activation and neurite elongation.
V. Bodrikov, I. Leshchyns'ka, V. Sytnyk, J. Overvoorde, J. den Hertog, and M. Schachner (2005)
J. Cell Biol. 168, 127-139
   Abstract »    Full Text »    PDF »
Receptor protein tyrosine phosphatase {alpha} is essential for hippocampal neuronal migration and long-term potentiation.
A. Petrone, F. Battaglia, C. Wang, A. Dusa, J. Su, D. Zagzag, R. Bianchi, P. Casaccia-Bonnefil, O. Arancio, and J. Sap (2003)
EMBO J. 22, 4121-4131
   Abstract »    Full Text »    PDF »
Dimerization In Vivo and Inhibition of the Nonreceptor Form of Protein Tyrosine Phosphatase Epsilon.
H. Toledano-Katchalski, Z. Tiran, T. Sines, G. Shani, S. Granot-Attas, J. den Hertog, and A. Elson (2003)
Mol. Cell. Biol. 23, 5460-5471
   Abstract »    Full Text »    PDF »
Nicotine Modulates the Expression of a Diverse Set of Genes in the Neuronal SH-SY5Y Cell Line.
T. Dunckley and R. J. Lukas (2003)
J. Biol. Chem. 278, 15633-15640
   Abstract »    Full Text »    PDF »
RPTP-{alpha} acts as a transducer of mechanical force on {alpha}v/{beta}3-integrin-cytoskeleton linkages.
G. von Wichert, G. Jiang, A. Kostic, K. De Vos, J. Sap, and M. P. Sheetz (2003)
J. Cell Biol. 161, 143-153
   Abstract »    Full Text »    PDF »
Redox-regulated Rotational Coupling of Receptor Protein-tyrosine Phosphatase alpha Dimers.
T. van der Wijk, C. Blanchetot, J. Overvoorde, and J. den Hertog (2003)
J. Biol. Chem. 278, 13968-13974
   Abstract »    Full Text »    PDF »
The Differentiation of Skeletal Muscle Cells Involves a Protein-tyrosine Phosphatase-alpha -mediated C-Src Signaling Pathway.
H. Lu, P. Shah, D. Ennis, G. Shinder, J. Sap, H. Le-Tien, and I. G. Fantus (2002)
J. Biol. Chem. 277, 46687-46695
   Abstract »    Full Text »    PDF »
VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts.
R. Nawroth, G. Poell, A. Ranft, S. Kloep, U. Samulowitz, G. Fachinger, M. Golding, D. T. Shima, U. Deutsch, and D. Vestweber (2002)
EMBO J. 21, 4885-4895
   Abstract »    Full Text »    PDF »
c-SRC Mediates Neurite Outgrowth through Recruitment of Crk to the Scaffolding Protein Sin/Efs without Altering the Kinetics of ERK Activation.
L.-T. Yang, K. Alexandropoulos, and J. Sap (2002)
J. Biol. Chem. 277, 17406-17414
   Abstract »    Full Text »    PDF »
Cosignaling of NCAM via lipid rafts and the FGF receptor is required for neuritogenesis.
P. Niethammer, M. Delling, V. Sytnyk, A. Dityatev, K. Fukami, and M. Schachner (2002)
J. Cell Biol. 157, 521-532
   Abstract »    Full Text »    PDF »
Two mechanisms activate PTP{alpha} during mitosis.
X.-M. Zheng and D. Shalloway (2001)
EMBO J. 20, 6037-6049
   Abstract »    Full Text »    PDF »
Contactin-Associated Protein (Caspr) and Contactin Form a Complex That Is Targeted to the Paranodal Junctions during Myelination.
J. C. Rios, C. V. Melendez-Vasquez, S. Einheber, M. Lustig, M. Grumet, J. Hemperly, E. Peles, and J. L. Salzer (2000)
J. Neurosci. 20, 8354-8364
   Abstract »    Full Text »    PDF »
Calmodulin Binds to and Inhibits the Activity of the Membrane Distal Catalytic Domain of Receptor Protein-tyrosine Phosphatase {alpha}.
L. Liang, K. L. Lim, K. T. Seow, C. H. Ng, and C. J. Pallen (2000)
J. Biol. Chem. 275, 30075-30081
   Abstract »    Full Text »    PDF »
Receptor-Like Protein Tyrosine Phosphatase alpha Homodimerizes on the Cell Surface.
G. Jiang, J. den Hertog, and T. Hunter (2000)
Mol. Cell. Biol. 20, 5917-5929
   Abstract »    Full Text »    PDF »
Emerging issues in receptor protein tyrosine phosphatase function: lifting fog or simply shifting?.
A. Petrone and J. Sap (2000)
J. Cell Sci. 113, 2345-2354
   Abstract »    PDF »
The Glycosylphosphatidyl Inositol-Anchored Adhesion Molecule F3/Contactin Is Required for Surface Transport of Paranodin/Contactin-Associated Protein (Caspr).
C. Faivre-Sarrailh, F. Gauthier, N. Denisenko-Nehrbass, A. Le Bivic, G. Rougon, and J.-A. Girault (2000)
J. Cell Biol. 149, 491-502
   Abstract »    Full Text »    PDF »
Calmodulin binds to and inhibits the activity of the membrane distal catalytic domain of receptor protein tyrosine phosphatase alpha (PTPa).
L. Liang, K. L. Lim, K. T. Seow, C. H. Ng, and C. J. Pallen (2000)
J. Biol. Chem.
   Abstract »
Regulation of Protein-tyrosine Phosphatases alpha and epsilon by Calpain-mediated Proteolytic Cleavage.
H. Gil-Henn, G. Volohonsky, and A. Elson (2001)
J. Biol. Chem. 276, 31772-31779
   Abstract »    Full Text »    PDF »
Cosignaling of NCAM via lipid rafts and the FGF receptor is required for neuritogenesis.
P. Niethammer, M. Delling, V. Sytnyk, A. Dityatev, K. Fukami, and M. Schachner (2002)
J. Cell Biol. 157, 521-532
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882