title: ADF/cofilin-mediated actin dynamics regulate AMPA receptor trafficking during synaptic plasticity.
abstract: Dendritic spines undergo actin-based growth and shrinkage during synaptic plasticity, in which the actin depolymerizing factor (ADF)/cofilin family of actin-associated proteins are important. Elevated ADF/cofilin activities often lead to reduced spine size and immature spine morphology but can also enhance synaptic potentiation in some cases. Thus, ADF/cofilin may have distinct effects on postsynaptic structure and function. We found that ADF/cofilin-mediated actin dynamics regulated AMPA receptor (AMPAR) trafficking during synaptic potentiation, which was distinct from actin's structural role in spine morphology. Specifically, elevated ADF/cofilin activity markedly enhanced surface addition of AMPARs after chemically induced long-term potentiation (LTP), whereas inhibition of ADF/cofilin abolished AMPAR addition. We found that chemically induced LTP elicited a temporal sequence of ADF/cofilin dephosphorylation and phosphorylation that underlies AMPAR trafficking and spine enlargement. These findings suggest that temporally regulated ADF/cofilin activities function in postsynaptic modifications of receptor number and spine size during synaptic plasticity.
authors.affiliation: Department of Cell Biology, Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Jiaping
authors.initials: J
authors.lastname: Gu
authors.forename: Chi Wai
authors.initials: CW
authors.lastname: Lee
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Fan
authors.forename: Daniel
authors.initials: D
authors.lastname: Komlos
authors.forename: Xin
authors.initials: X
authors.lastname: Tang
authors.forename: Chicheng
authors.initials: C
authors.lastname: Sun
authors.forename: Kuai
authors.initials: K
authors.lastname: Yu
authors.forename: H Criss
authors.initials: HC
authors.lastname: Hartzell
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
authors.forename: James R
authors.initials: JR
authors.lastname: Bamburg
authors.forename: James Q
authors.initials: JQ
authors.lastname: Zheng
mesh_terms: D051339:Actin Depolymerizing Factors / Q000235:genetics / Q000502:physiology*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001703:Biophysics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011247:Pregnancy; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology; D053778:Thiazolidines / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection / Q000379:methods; D000097573:Red Fluorescent Protein
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018691:Excitatory Amino Acid Antagonists; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D026902:Potassium Channel Blockers; D018091:Receptors, AMPA; D019789:Tetraethylammonium; D053778:Thiazolidines; D000097573:Red Fluorescent Protein; C037067:latrunculin A