title: Cortactin-binding protein 2 increases microtubule stability and regulates dendritic arborization.
abstract: Neurons are characterized by subcellular compartments, such as axons, dendrites and synapses, that have highly specialized morphologies and biochemical specificities. Cortactin-binding protein 2 (CTTNBP2), a neuron-specific F-actin regulator, has been shown to play a role in the regulation of dendritic spine formation and their maintenance. Here, we show that, in addition to F-actin, CTTNBP2 also associates with microtubules before mature dendritic spines form. This association of CTTNBP2 and microtubules induced the formation of microtubule bundles. Although the middle (Mid) region of CTTNBP2 was sufficient for its association with microtubules, for microtubule bundling, the N-terminal region containing the coiled-coil motifs (NCC), which mediates the dimerization or oligomerization of CTTNBP2, was also required. Our study indicates that CTTNBP2 proteins form a dimer or oligomer and brings multiple microtubule filaments together to form bundles. In cultured hippocampal neurons, knockdown of CTTNBP2 or expression of the Mid or NCC domain alone reduced the acetylation levels of microtubules and impaired dendritic arborization. This study suggests that CTTNBP2 influences both the F-actin and microtubule cytoskeletons and regulates dendritic spine formation and dendritic arborization.
authors.affiliation: Faculty of Life Sciences, Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Pu-Yun
authors.initials: PY
authors.lastname: Shih
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Sue-Ping
authors.initials: SP
authors.lastname: Lee
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Yi-Kai
authors.initials: YK
authors.lastname: Chen
authors.affiliation: Faculty of Life Sciences, Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan yph@gate.sinica.edu.tw.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Hsueh
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins; D008870:Microtubules / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats
chemical_list: C442860:CTTNBP2 protein, human; D002352:Carrier Proteins; C115999:Cttnbp2 protein, rat; D003598:Cytoskeletal Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins
keywords: Acetylated tubulin; CTTNBP2; Dendritic arborization; Microtubule bundling