title: Cortactin-binding protein 2 modulates the mobility of cortactin and regulates dendritic spine formation and maintenance.
abstract: Dendritic spines, the actin-rich protrusions emerging from dendrites, are the locations of excitatory synapses in mammalian brains. Many molecules that regulate actin dynamics also influence the morphology and/or density of dendritic spines. Since dendritic spines are neuron-specific subcellular structures, neuron-specific proteins or signals are expected to control spinogenesis. In this report, we characterize the distribution and function of neuron-predominant cortactin-binding protein 2 (CTTNBP2) in rodents. An analysis of an Expressed Sequence Tag database revealed three splice variants of mouse CTTNBP2: short, long, and intron. Immunoblotting indicated that the short form is the dominant CTTNBP2 variant in the brain. CTTNBP2 proteins were highly concentrated at dendritic spines in cultured rat hippocampal neurons as well as in the mouse brain. Knockdown of CTTNBP2 in neurons reduced the density and size of dendritic spines. Consistent with these morphological changes, the frequencies of miniature EPSCs in CTTNBP2 knockdown neurons were lower than those in control neurons. Cortactin acts downstream of CTTNBP2 in spinogenesis, as the defects caused by CTTNBP2 knockdown were rescued by overexpression of cortactin but not expression of a CTTNBP2 mutant protein lacking the cortactin interaction. Finally, immunofluorescence staining demonstrated that, unlike cortactin, CTTNBP2 stably resided at dendritic spines even after glutamate stimulation. Fluorescence recovery after photobleaching further suggested that CTTNBP2 modulates the mobility of cortactin in neurons. CTTNBP2 may thus help to immobilize cortactin in dendritic spines and control the density of dendritic spines.
authors.affiliation: Molecular Cell Biology, Taiwan International Graduate Program, Institute of Molecular Biology, Academia Sinica, and Graduate Institute of Life Sciences, National Defense Medical Center, and Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan 115, Republic of China.
authors.forename: Yi-Kai
authors.initials: YK
authors.lastname: Chen
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Hsueh
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D051356:Cortactin / Q000378:metabolism*; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism*; D004622:Embryo, Mammalian; D018846:Excitatory Amino Acids / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005260:Female; D036681:Fluorescence Recovery After Photobleaching; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins; D035683:MicroRNAs / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D018408:Patch-Clamp Techniques; D051381:Rats; D013569:Synapses / Q000378:metabolism; D013997:Time Factors; D014162:Transfection / Q000379:methods
chemical_list: D000199:Actins; C442860:CTTNBP2 protein, human; D002352:Carrier Proteins; D051356:Cortactin; D018846:Excitatory Amino Acids; D008164:Luminescent Proteins; D026901:Membrane Transport Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins