A contactin-receptor-like protein tyrosine phosphatase β complex mediates adhesive communication between astroglial cells and gonadotrophin-releasing hormone neurones

A. S. Parent, A. E. Mungenast, A. Lomniczi, U. S. Sandau, E. Peles, M. A. Bosch, O. K. Rønnekleiv, Segio R. Ojeda

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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 β (RPTPβ), 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 RPTPβ mRNA predominantly expressed in hypothalamic astrocytes encodes an RPTPβ isoform (short RPTPβ) 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 RPTPβ, and this adhesiveness is blocked when contactin GPI anchoring is disrupted or contactin binding capacity is immunoneutralised, suggesting that astrocytic RPTPβ interacts with neuronal contactin to mediate glial-GnRH neurone adhesiveness. Because the abundance of short RPTPβ 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 RPTPβ-contactin is a dynamic mechanism of neurone-glia communication during female sexual development.

Original languageEnglish (US)
Pages (from-to)847-859
Number of pages13
JournalJournal of Neuroendocrinology
Volume19
Issue number11
DOIs
StatePublished - Nov 2007

Keywords

  • Adhesion molecules
  • Astrocytes
  • GnRH neurones
  • Hypothalamus

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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