The Synaptic Cell Adhesion Molecule, SynCAM1, Mediates Astrocyte-to-Astrocyte and Astrocyte-to-GnRH Neuron Adhesiveness in the Mouse Hypothalamus
Year: 2011
Type: article
Abstract: We previously identified synaptic cell adhesion molecule 1 (SynCAM1) as a component of a genetic network involved in the hypothalamic control of female puberty. Although it is well established that SynCAM1 is a synaptic adhesion molecule, its contribution to hypothalamic function is unknown. Here we show that, in addition to the expected neuronal localization illustrated by its presence in GnRH neurons, SynCAM1 is expressed in hypothalamic astrocytes. Cell adhesion assays indicated that SynCAM is recognized by both GnRH neurons and astrocytes as an adhesive partner and promotes cell-cell adhesiveness via homophilic, extracellular domain-mediated interactions. Alternative splicing of the SynCAM1 primary mRNA transcript yields four mRNAs encoding membrane-spanning SynCAM1 isoforms. Variants 1 and 4 are predicted to be both N and O glycosylated. Hypothalamic astrocytes and GnRH-producing GT1-7 cells express mainly isoform 4 mRNA, and sequential N- and O-deglycosylation of proteins extracted from these cells yields progressively smaller SynCAM1 species, indicating that isoform 4 is the predominant SynCAM1 variant expressed in astrocytes and GT1-7 cells. Neither cell type expresses the products of two other SynCAM genes (SynCAM2 and SynCAM3), suggesting that SynCAM-mediated astrocyte-astrocyte and astrocyte-GnRH neuron adhesiveness is mostly mediated by SynCAM1 homophilic interactions. When erbB4 receptor function is disrupted in astrocytes, via transgenic expression of a dominant-negative erbB4 receptor form, SynCAM1-mediated adhesiveness is severely compromised. Conversely, SynCAM1 adhesive behavior is rapidly, but transiently, enhanced in astrocytes by ligand-dependent activation of erbB4 receptors, suggesting that erbB4-mediated events affecting SynCAM1 function contribute to regulate astrocyte adhesive communication.
Source: Endocrinology
DOI: 10.1210/en.2010-1434
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Massachusetts Institute of Technology, Portland State University, National Alliance for Research on Schizophrenia and Depression, National Institutes of Health, Oregon National Primate Research Center, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Reproductive Biology-Multidisciplinary, Cooperative Research on Infertility in Primates, Molecular Specifiers of Neural Cell Plasticity, G2504117740, Multidisciplinary Training in Neuroendocrinology, G2834756128, SUPPORT FOR NATIONAL PRIMATE RESEARCH CENTER, G3171584995, G3938696996, Mechanisms of SynCAM-Induced Synapse Formation, G5007525772, Molecular Basis of Neuron-Gila Interactions in the CNS, REPRODUCTIVE STEROIDS AND EXPERIMENTAL STROKE, Neuroendocrinology of Puberty and Sexual Development, G9000032359, G9000104972
OpenAlex ID: W2079083712