title: DDA3 stabilizes microtubules and suppresses neurite formation.
abstract: We have previously shown that DDA3 - also known as proline/serine-rich coiled-coil protein 1 (PSRC1) - is a microtubule-associated protein that promotes cell growth by stimulating the β-catenin pathway. Here, we report that DDA3 can bundle and stabilize microtubules in vivo and in vitro. We found that overexpression of DDA3 increased the abundance of acetylated and tyrosinated microtubules. We employed PC12 and N2a cell lines, as well as cultured hippocampal neurons, and demonstrated that overexpression of DDA3 suppressed neurite/axon outgrowth, whereas its depletion accelerated neurite/axon formation and elongation. Knockdown of DDA3 reduced β3-tubulin levels in N2a cells, which contributed to the spontaneous neurite formation caused by DDA3 depletion. Consistent with its role in suppressing neuritogenesis, DDA3 was downregulated during induced neuronal differentiation. Moreover, expression of DDA3 was detected in the rat brain at embryonic (E) day E15 and in the cortical region at E17, the period of active neurogenesis. Levels of cortical DDA3 decreased at the beginning of E19, when active neuritogenesis is completed. Overall our results demonstrate that DDA3 is a so-far-unknown microtubule-stabilizing protein that is involved in regulating neurite formation and elongation.
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Pei-Chen
authors.initials: PC
authors.lastname: Hsieh
authors.forename: Ming-Lun
authors.initials: ML
authors.lastname: Chiang
authors.forename: Jui-Chun
authors.initials: JC
authors.lastname: Chang
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Yan
authors.forename: Fung-Fang
authors.initials: FF
authors.lastname: Wang
authors.forename: Yun-Chia
authors.initials: YC
authors.lastname: Chou
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D041681:NIH 3T3 Cells; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016716:PC12 Cells; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010750:Phosphoproteins; C403261:Psrc1 protein, mouse