title: A contactin-receptor-like protein tyrosine phosphatase beta complex mediates adhesive communication between astroglial cells and gonadotrophin-releasing hormone neurones.
abstract: Although it is well established that gonadotrophin-releasing hormone (GnRH) neurones and astrocytes maintain an intimate contact throughout development and adult life, the cell-surface molecules that may contribute to this adhesiveness remain largely unknown. In the peripheral nervous system, the glycosylphosphatidyl inositol (GPI)-anchored protein contactin is a cell-surface neuronal protein required for axonal-glial adhesiveness. A glial transmembrane protein recognised by neuronal contactin is receptor-like protein tyrosine phosphatase beta (RPTP beta), a phosphatase with structural similarities to cell adhesion molecules. In the present study, we show that contactin, and its preferred in cis partner Caspr1, are expressed in GnRH neurones. We also show that the RPTP beta mRNA predominantly expressed in hypothalamic astrocytes encodes an RPTP beta isoform (short RPTP beta) that uses its carbonic anhydrase (CAH) extracellular subdomain to interact with neuronal contactin. Immunoreactive contactin is most abundant in GnRH nerve terminals projecting to both the organum vasculosum of the lamina terminalis and median eminence, implying GnRH axons as an important site of contactin-dependent cell adhesiveness. GT1-7 immortalised GnRH neurones adhere to the CAH domain of RPTPbeta, and this adhesiveness is blocked when contactin GPI anchoring is disrupted or contactin binding capacity is immunoneutralised, suggesting that astrocytic RPTP beta interacts with neuronal contactin to mediate glial-GnRH neurone adhesiveness. Because the abundance of short RPTP beta mRNA increases in the female mouse hypothalamus (but not in the cerebral cortex) before puberty, it appears that an increased interaction between GnRH axons and astrocytes mediated by RPTP beta-contactin is a dynamic mechanism of neurone-glia communication during female sexual development.
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR 97006, USA.
authors.forename: A-S
authors.initials: AS
authors.lastname: Parent
authors.forename: A E
authors.initials: AE
authors.lastname: Mungenast
authors.forename: A
authors.initials: A
authors.lastname: Lomniczi
authors.forename: U S
authors.initials: US
authors.lastname: Sandau
authors.forename: E
authors.initials: E
authors.lastname: Peles
authors.forename: M A
authors.initials: MA
authors.lastname: Bosch
authors.forename: O K
authors.initials: OK
authors.lastname: Rønnekleiv
authors.forename: S R
authors.initials: SR
authors.lastname: Ojeda
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D058966:Contactins; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C491322:Cntnap1 protein, mouse; D058966:Contactins; D011993:Recombinant Fusion Proteins; D007987:Gonadotropin-Releasing Hormone; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5