Structural basis for interactions between contactin family members and protein-tyrosine phosphatase receptor type G in neural tissues

Roman M. Nikolaienko, Michal Hammel, Véronique Dubreuil, Rana Zalmai, David R. Hall, Nurjahan Mehzabeen, Sebastian J. Karuppan, Sheila Harroch, Salvatore Stella, Samuel Bouyain

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)21335-21349
Number of pages15
JournalJournal of Biological Chemistry
Volume291
Issue number41
DOIs
StatePublished - Oct 7 2016

Fingerprint

Contactins
Class 5 Receptor-Like Protein Tyrosine Phosphatases
Tissue
Retinal Rod Photoreceptor Cells
Cell Adhesion Molecules
Neurology
Electric wiring
Nervous System
Conformations
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Nikolaienko, R. M., Hammel, M., Dubreuil, V., Zalmai, R., Hall, D. R., Mehzabeen, N., ... Bouyain, S. (2016). Structural basis for interactions between contactin family members and protein-tyrosine phosphatase receptor type G in neural tissues. Journal of Biological Chemistry, 291(41), 21335-21349. https://doi.org/10.1074/jbc.M116.742163
Nikolaienko, Roman M. ; Hammel, Michal ; Dubreuil, Véronique ; Zalmai, Rana ; Hall, David R. ; Mehzabeen, Nurjahan ; Karuppan, Sebastian J. ; Harroch, Sheila ; Stella, Salvatore ; Bouyain, Samuel. / Structural basis for interactions between contactin family members and protein-tyrosine phosphatase receptor type G in neural tissues. In: Journal of Biological Chemistry. 2016 ; Vol. 291, No. 41. pp. 21335-21349.
@article{29ec1913267a462aa8981e49efe11698,
title = "Structural basis for interactions between contactin family members and protein-tyrosine phosphatase receptor type G in neural tissues",
abstract = "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.",
author = "Nikolaienko, {Roman M.} and Michal Hammel and V{\'e}ronique Dubreuil and Rana Zalmai and Hall, {David R.} and Nurjahan Mehzabeen and Karuppan, {Sebastian J.} and Sheila Harroch and Salvatore Stella and Samuel Bouyain",
year = "2016",
month = "10",
day = "7",
doi = "10.1074/jbc.M116.742163",
language = "English (US)",
volume = "291",
pages = "21335--21349",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "41",

}

Nikolaienko, RM, Hammel, M, Dubreuil, V, Zalmai, R, Hall, DR, Mehzabeen, N, Karuppan, SJ, Harroch, S, Stella, S & Bouyain, S 2016, 'Structural basis for interactions between contactin family members and protein-tyrosine phosphatase receptor type G in neural tissues', Journal of Biological Chemistry, vol. 291, no. 41, pp. 21335-21349. https://doi.org/10.1074/jbc.M116.742163

Structural basis for interactions between contactin family members and protein-tyrosine phosphatase receptor type G in neural tissues. / Nikolaienko, Roman M.; Hammel, Michal; Dubreuil, Véronique; Zalmai, Rana; Hall, David R.; Mehzabeen, Nurjahan; Karuppan, Sebastian J.; Harroch, Sheila; Stella, Salvatore; Bouyain, Samuel.

In: Journal of Biological Chemistry, Vol. 291, No. 41, 07.10.2016, p. 21335-21349.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Structural basis for interactions between contactin family members and protein-tyrosine phosphatase receptor type G in neural tissues

AU - Nikolaienko, Roman M.

AU - Hammel, Michal

AU - Dubreuil, Véronique

AU - Zalmai, Rana

AU - Hall, David R.

AU - Mehzabeen, Nurjahan

AU - Karuppan, Sebastian J.

AU - Harroch, Sheila

AU - Stella, Salvatore

AU - Bouyain, Samuel

PY - 2016/10/7

Y1 - 2016/10/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84990895382&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84990895382&partnerID=8YFLogxK

U2 - 10.1074/jbc.M116.742163

DO - 10.1074/jbc.M116.742163

M3 - Article

C2 - 27539848

AN - SCOPUS:84990895382

VL - 291

SP - 21335

EP - 21349

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 41

ER -