skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Structural Basis for Interactions Between Contactin Family Members and Protein-tyrosine Phosphatase Receptor Type G in Neural Tissues

Journal Article · · Journal of Biological Chemistry
 [1];  [2];  [3];  [1];  [1];  [1];  [1];  [4];  [5];  [1]
  1. Univ. of Missouri, Kansas City, MO (United States)
  2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  3. Inst. Pasteur de Paris (France); Univ. Paris Diderot (France)
  4. Univ. Paris Diderot (France)
  5. Univ. of Missouri, Kansas City, MO (United States). School of Medicine

Protein-tyrosine phosphatase receptor type G (RPTPγ/PTPRG) interacts in vitro with contactin-3-6 (CNTN3-6), a group of glycophosphatidylinositol-anchored cell adhesion molecules involved in the wiring of the nervous system. In addition to PTPRG, CNTNs associate with multiple transmembrane proteins and signal inside the cell via cis-binding partners to alleviate the absence of an intracellular region. Here, we use comprehensive biochemical and structural analyses to demonstrate that PTPRG·CNTN3-6 complexes share similar binding affinities and a conserved arrangement. Furthermore, as a first step to identifying PTPRG·CNTN complexes in vivo, we found that PTPRG and CNTN3 associate in the outer segments of mouse rod photoreceptor cells. In particular, PTPRG and CNTN3 form cis-complexes at the surface of photoreceptors yet interact in trans when expressed on the surfaces of apposing cells. Further structural analyses suggest that all CNTN ectodomains adopt a bent conformation and might lie parallel to the cell surface to accommodate these cis and trans binding modes. Taken together, these studies identify a PTPRG·CNTN complex in vivo and provide novel insights into PTPRG- and CNTN-mediated signaling.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1408402
Journal Information:
Journal of Biological Chemistry, Vol. 291, Issue 41; ISSN 0021-9258
Publisher:
American Society for Biochemistry and Molecular BiologyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 25 works
Citation information provided by
Web of Science

References (60)

Shape Complementarity at Protein/Protein Interfaces journal December 1993
Uniqueness of ab initio shape determination in small-angle scattering journal April 2003
Neurofascin Is a Glial Receptor for the Paranodin/Caspr-Contactin Axonal Complex at the Axoglial Junction journal February 2002
Overview of the CCP 4 suite and current developments journal March 2011
DAMMIF, a program for rapid ab-initio shape determination in small-angle scattering journal January 2009
Contactins: Emerging key roles in the development and function of the nervous system journal January 2009
Structural Model and trans-Interaction of the Entire Ectodomain of the Olfactory Cell Adhesion Molecule journal February 2011
The Crystal Structure of the α-Neurexin-1 Extracellular Region Reveals a Hinge Point for Mediating Synaptic Adhesion and Function journal June 2011
Electron tomography of paranodal septate-like junctions and the associated axonal and glial cytoskeletons in the central nervous system journal December 2010
The Structure of Neurexin 1α Reveals Features Promoting a Role as Synaptic Organizer journal June 2011
Advances and pitfalls of protein structural alignment journal June 2009
Contactin-4 Mediates Axon-Target Specificity and Functional Development of the Accessory Optic System journal May 2015
BIG-1: A new TAG-1/F3-related member of the immunoglobulin superfamily with neurite outgrowth-promoting activity journal August 1994
Accurate SAXS Profile Computation and its Assessment by Contrast Variation Experiments journal August 2013
A mechanistic basis for converting a receptor tyrosine kinase agonist to an antagonist journal September 2007
A time- and cost-efficient system for high-level protein production in mammalian cells journal September 2006
Deficiency of neural recognition molecule NB-2 affects the development of glutamatergic auditory pathways from the ventral cochlear nucleus to the superior olivary complex in mouse journal December 2009
Molecular Mechanisms of Synaptic Specificity in Developing Neural Circuits journal October 2010
The HSPGs Syndecan and Dallylike Bind the Receptor Phosphatase LAR and Exert Distinct Effects on Synaptic Development journal February 2006
Inference of Macromolecular Assemblies from Crystalline State journal September 2007
UCSF Chimera?A visualization system for exploratory research and analysis journal January 2004
Neuropilins lock secreted semaphorins onto plexins in a ternary signaling complex journal October 2012
Robust, high-throughput solution structural analyses by small angle X-ray scattering (SAXS) journal July 2009
No Obvious Abnormality in Mice Deficient in Receptor Protein Tyrosine Phosphatase beta journal October 2000
BIG-2 Mediates Olfactory Axon Convergence to Target Glomeruli journal March 2008
Interaction of amyloid precursor protein with contactins and NgCAM in the retinotectal system journal February 2008
Modulation of Rod Photoreceptor Cyclic Nucleotide-Gated Channels by Tyrosine Phosphorylation journal December 1997
Receptor protein tyrosine phosphatases are expressed by cycling retinal progenitor cells and involved in neuronal development of mouse retina journal March 2008
Neuronal Ig/Caspr Recognition Promotes the Formation of Axoaxonic Synapses in Mouse Spinal Cord journal January 2014
Distribution of different isoforms of receptor protein tyrosine phosphatase γ (Ptprg-RPTP γ) in adult mouse brain: upregulation during neuroinflammation journal March 2013
Proteoglycan-Specific Molecular Switch for RPTP  Clustering and Neuronal Extension journal March 2011
Receptor protein tyrosine phosphatases regulate neural development and axon guidance journal November 2004
Growth factors regulate phototransduction in retinal rods by modulating cyclic nucleotide-gated channels through dephosphorylation of a specific tyrosine residue journal April 2001
Receptor Protein Tyrosine Phosphatase   Is a Marker for Pyramidal Cells and Sensory Neurons in the Nervous System and Is Not Necessary for Normal Development journal June 2006
Synaptic formation in subsets of glutamatergic terminals in the mouse hippocampal formation is affected by a deficiency in the neural cell recognition molecule NB-3 journal April 2010
A Contactin–Receptor-Like Protein Tyrosine Phosphatase β Complex Mediates Adhesive Communication Between Astroglial Cells and Gonadotrophin-Releasing Hormone Neurones journal November 2007
Coot model-building tools for molecular graphics journal November 2004
Transient Mammalian Cell Transfection with Polyethylenimine (PEI) book January 2013
Structural basis for extracellular cis and trans RPTPσ signal competition in synaptogenesis journal November 2014
A cis-complex of NB-2/contactin-5 with amyloid precursor-like protein 1 is localized on the presynaptic membrane journal February 2012
VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation journal April 2013
Fiji: an open-source platform for biological-image analysis journal June 2012
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Crystal structure of Caenorhabditis elegans HER-1 and characterization of the interaction between HER-1 and TRA-2A journal August 2004
Ephrin-Mediated cis-Attenuation of Eph Receptor Signaling Is Essential for Spinal Motor Axon Guidance journal July 2011
Contactins book January 2011
Structural basis for Notch1 engagement of Delta-like 4 journal February 2015
Direct observation of individual endogenous protein complexes in situ by proximity ligation journal October 2006
A complex between contactin-1 and the protein tyrosine phosphatase PTPRZ controls the development of oligodendrocyte precursor cells journal October 2011
Structure-based mutagenesis of the substrate-recognition domain of Nrdp1/FLRF identifies the binding site for the receptor tyrosine kinase ErbB3 journal February 2007
Cis–trans interactions of cell surface receptors: biological roles and structural basis journal August 2011
Upgrading SELEX Technology by Using Lambda Exonuclease Digestion for Single-Stranded DNA Generation journal December 2009
NMRPipe: A multidimensional spectral processing system based on UNIX pipes journal November 1995
Activity-Dependent Modulation of Rod Photoreceptor Cyclic Nucleotide-Gated Channels Mediated by Phosphorylation of a Specific Tyrosine Residue journal June 1999
The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules journal January 2010
Identification of a carbonic anhydrase-like domain in the extracellular region of RPTP gamma defines a new subfamily of receptor tyrosine phosphatases. journal March 1993
Phaser crystallographic software journal July 2007
Association of Shank 1A Scaffolding Protein with Cone Photoreceptor Terminals in the Mammalian Retina journal September 2012
Neural recognition molecules CHL1 and NB-3 regulate apical dendrite orientation in the neocortex via PTPα journal November 2007
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997

Cited By (7)

Architecture of cell–cell adhesion mediated by sidekicks journal August 2018
Affinity capture of polyribosomes followed by RNAseq (ACAPseq), a discovery platform for protein-protein interactions journal October 2018
Genetic study links components of the autonomous nervous system to heart-rate profile during exercise journal March 2018
Keratan sulfate ( KS )‐proteoglycans and neuronal regulation in health and disease: the importance of KS ‐glycodynamics and interactive capability with neuroregulatory ligands journal January 2019
Latrophilin’s Social Protein Network journal June 2019
Defining the binding interface of Amyloid Precursor Protein (APP) and Contactin3 (CNTN3) by site-directed mutagenesis journal July 2019
Genetic study links components of the autonomous nervous system to heart-rate profile during exercise journal October 2017

Similar Records

Related Subjects