title: Plasticity-related gene 5 promotes spine formation in murine hippocampal neurons.
abstract: The transmembrane protein plasticity-related genes 3 and 5 (PRG3 and PRG5) increase filopodial formation in various cell lines, independently of Cdc42. However, information on the effects of PRG5 during neuronal development is sparse. Here, we present several lines of evidence for the involvement of PRG5 in the genesis and stabilization of dendritic spines. First, PRG5 was strongly expressed during mouse brain development from embryonic day 14 (E14), peaked around the time of birth, and remained stable at least until early adult stages (i.e. P30). Second, on a subcellular level, PRG5 expression shifted from an equal distribution along all neurites toward accumulation only along dendrites during hippocampal development in vitro. Third, overexpression of PRG5 in immature hippocampal neurons induced formation of spine-like structures ahead of time. Proper amino acid sequences in the extracellular domains (D1 to D3) of PRG5 were a prerequisite for trafficking and induction of spine-like structures, as shown by mutation analysis. Fourth, at stages when spines are present, knockdown of PRG5 reduced the number but not the length of protrusions. This was accompanied by a decrease in the number of excitatory synapses and, consequently, by a reduction of miniature excitatory postsynaptic current frequencies, although miniature excitatory postsynaptic current amplitudes remained similar. In turn, overexpressing PRG5 in mature neurons not only increased Homer-positive spine numbers but also augmented spine head diameters. Mechanistically, PRG5 interacts with phosphorylated phosphatidylinositols, phospholipids involved in dendritic spine formation by different lipid-protein assays. Taken together, our data propose that PRG5 promotes spine formation.
authors: From the Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: Pierluca
authors: P
authors: Coiro
authors: From the Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: Luminita
authors: L
authors: Stoenica
authors: From the Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors: Ulf
authors: U
authors: Strauss
authors: From the Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany anja.braeuer@charite.de.
authors: Anja Ursula
authors: AU
authors: Bräuer
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000235:genetics* / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006624:Hippocampus / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology
chemical_list: D008565:Membrane Proteins; C550842:plasticity-related gene 5 protein, mouse; D010744:Phosphoric Monoester Hydrolases
keywords: Cell Biology; Cell Differentiation; Dendritic Spine; Membrane Protein; Phosphatidylinositol Phosphatase