title: Neuronal profilins in health and disease: Relevance for spine plasticity and Fragile X syndrome.
abstract: Learning and memory, to a large extent, depend on functional changes at synapses. Actin dynamics orchestrate the formation of synapses, as well as their stabilization, and the ability to undergo plastic changes. Hence, profilins are of key interest as they bind to G-actin and enhance actin polymerization. However, profilins also compete with actin nucleators, thereby restricting filament formation. Here, we provide evidence that the two brain isoforms, profilin1 (PFN1) and PFN2a, regulate spine actin dynamics in an opposing fashion, and that whereas both profilins are needed during synaptogenesis, only PFN2a is crucial for adult spine plasticity. This finding suggests that PFN1 is the juvenile isoform important during development, whereas PFN2a is mandatory for spine stability and plasticity in mature neurons. In line with this finding, only PFN1 levels are altered in the mouse model of the developmental neurological disorder Fragile X syndrome. This finding is of high relevance because Fragile X syndrome is the most common monogenetic cause for autism spectrum disorder. Indeed, the expression of recombinant profilins rescued the impairment in spinogenesis, a hallmark in Fragile X syndrome, thereby linking the regulation of actin dynamics to synapse development and possible dysfunction.
authors.affiliation: Division of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig, D-38106 Braunschweig, Germany;
authors.forename: Kristin
authors.initials: K
authors.lastname: Michaelsen-Preusse
authors.affiliation: Division of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig, D-38106 Braunschweig, Germany;
authors.forename: Sabine
authors.initials: S
authors.lastname: Zessin
authors.affiliation: Division of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig, D-38106 Braunschweig, Germany;
authors.forename: Gayane
authors.initials: G
authors.lastname: Grigoryan
authors.affiliation: Division of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig, D-38106 Braunschweig, Germany;
authors.forename: Franziska
authors.initials: F
authors.lastname: Scharkowski
authors.affiliation: Division of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig, D-38106 Braunschweig, Germany;
authors.forename: Jonas
authors.initials: J
authors.lastname: Feuge
authors.affiliation: Division of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig, D-38106 Braunschweig, Germany; Helmholtz Centre for Infection Research, AG Neuroinflammation and Neurodegeneration, 38124 Braunschweig, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Remus
authors.affiliation: Division of Cellular Neurobiology, Zoological Institute, Technische Universität Braunschweig, D-38106 Braunschweig, Germany; Helmholtz Centre for Infection Research, AG Neuroinflammation and Neurodegeneration, 38124 Braunschweig, Germany m.korte@tu-bs.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Korte
mesh_terms: D000818:Animals; D005600:Fragile X Syndrome / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism*; D051304:Profilins / Q000378:metabolism*
chemical_list: D051304:Profilins
keywords: FMRP; FXS; actin; profilin; spinogenesis