title: cpg15 and cpg15-2 constitute a family of activity-regulated ligands expressed differentially in the nervous system to promote neurite growth and neuronal survival.
abstract: Many ligands that affect nervous system development are members of gene families that function together to coordinate the assembly of complex neural circuits. cpg15/neuritin encodes an extracellular ligand that promotes neurite growth, neuronal survival, and synaptic maturation. Here we identify cpg15-2 as the only paralogue of cpg15 in the mouse and human genome. Both genes are expressed predominantly in the nervous system, where their expression is regulated by activity. cpg15-2 expression increases by more than twofold in response to kainate-induced seizures and nearly fourfold in the visual cortex in response to 24 hours of light exposure following dark adaptation. cpg15 and cpg15-2 diverge in their spatial and temporal expression profiles. cpg15-2 mRNA is most abundant in the retina and the olfactory bulb, as opposed to the cerebral cortex and the hippocampus for cpg15. In the retina, they differ in their cell-type specificity. cpg15 is expressed in retinal ganglion cells, whereas cpg15-2 is predominantly in bipolar cells. Developmentally, onset of cpg15-2 expression is delayed compared with cpg15 expression. CPG15-2 is glycosylphosphatidylinositol (GPI) anchored to the cell membrane and, like CPG15, can be released in a soluble-secreted form, but with lower efficiency. CPG15 and CPG15-2 were found to form homodimers and heterodimers with each other. In hippocampal explants and dissociated cultures, CPG15 and CPG15-2 promote neurite growth and neuronal survival with similar efficacy. Our findings suggest that CPG15 and CPG15-2 perform similar cellular functions but may play distinct roles in vivo through their cell-type- and tissue-specific transcriptional regulation.
authors.affiliation: The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Fujino
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wu
authors.forename: Walter C
authors.initials: WC
authors.lastname: Lin
authors.forename: Marnie A
authors.initials: MA
authors.lastname: Phillips
authors.forename: Elly
authors.initials: E
authors.lastname: Nedivi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D003623:Dark Adaptation / Q000502:physiology; D058851:GPI-Linked Proteins; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000378:metabolism; D014162:Transfection
chemical_list: D058851:GPI-Linked Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C484377:Nrn1 protein, mouse; D020033:Protein Isoforms