title: Actin Tyrosine-53-Phosphorylation in Neuronal Maturation and Synaptic Plasticity.
abstract: Rapid reorganization and stabilization of the actin cytoskeleton in dendritic spines enables cellular processes underlying learning, such as long-term potentiation (LTP). Dendritic spines are enriched in exceptionally short and dynamic actin filaments, but the studies so far have not revealed the molecular mechanisms underlying the high actin dynamics in dendritic spines. Here, we show that actin in dendritic spines is dynamically phosphorylated at tyrosine-53 (Y53) in rat hippocampal and cortical neurons. Our findings show that actin phosphorylation increases the turnover rate of actin filaments and promotes the short-term dynamics of dendritic spines. During neuronal maturation, actin phosphorylation peaks at the first weeks of morphogenesis, when dendritic spines form, and the amount of Y53-phosphorylated actin decreases when spines mature and stabilize. Induction of LTP transiently increases the amount of phosphorylated actin and LTP induction is deficient in neurons expressing mutant actin that mimics phosphorylation. Actin phosphorylation provides a molecular mechanism to maintain the high actin dynamics in dendritic spines during neuronal development and to induce fast reorganization of the actin cytoskeleton in synaptic plasticity. In turn, dephosphorylation of actin is required for the stabilization of actin filaments that is necessary for proper dendritic spine maturation and LTP maintenance.
  
  
  
  Dendritic spines are small protrusions from neuronal dendrites where the postsynaptic components of most excitatory synapses reside. Precise control of dendritic spine morphology and density is critical for normal brain function. Accordingly, aberrant spine morphology is linked to many neurological diseases. The actin cytoskeleton is a structural element underlying the proper morphology of dendritic spines. Therefore, defects in the regulation of the actin cytoskeleton in neurons have been implicated in neurological diseases. Here, we revealed a novel mechanism for regulating neuronal actin cytoskeleton that explains the specific organization and dynamics of actin in spines. The better we understand the regulation of the dendritic spine morphology, the better we understand what goes wrong in neurological diseases.
authors.affiliation: Neuroscience Center and Minerva Institute for Medical Research, 00290 Helsinki, Finland, and.
authors.forename: Enni
authors.initials: E
authors.lastname: Bertling
authors.affiliation: Neuroscience Center and Department of Biosciences, Physiology and Neuroscience, and.
authors.forename: Jonas
authors.initials: J
authors.lastname: Englund
authors.affiliation: Neuroscience Center and Minerva Institute for Medical Research, 00290 Helsinki, Finland, and.
authors.forename: Rimante
authors.identifier: 0000-0003-1017-1172
authors.initials: R
authors.lastname: Minkeviciene
authors.affiliation: Neuroscience Center and Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Mikko
authors.initials: M
authors.lastname: Koskinen
authors.affiliation: Department of Biosciences, Physiology and Neuroscience, and.
authors.forename: Mikael
authors.initials: M
authors.lastname: Segerstråle
authors.affiliation: Neuroscience Center and.
authors.forename: Eero
authors.identifier: 0000-0002-1402-2791
authors.initials: E
authors.lastname: Castrén
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Tomi
authors.initials: T
authors.lastname: Taira
authors.affiliation: Neuroscience Center and Minerva Institute for Medical Research, 00290 Helsinki, Finland, and pirta.hotulainen@helsinki.fi.
authors.forename: Pirta
authors.identifier: 0000-0003-0764-8582
authors.initials: P
authors.lastname: Hotulainen
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006801:Humans; D017774:Long-Term Potentiation; D008297:Male; D055495:Neurogenesis; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000199:Actins; D014443:Tyrosine
keywords: LTP; actin cytoskeleton; dendritic spines; phosphorylation; spinogenesis; synaptic plasticity