title: The Angelman syndrome protein Ube3a is required for polarized dendrite morphogenesis in pyramidal neurons.
abstract: Pyramidal neurons have a highly polarized dendritic morphology, characterized by one long apical dendrite and multiple short basal dendrites. They function as the primary excitatory cells of the mammalian prefrontal cortex and the corticospinal tract. However, the molecular mechanisms underlying the development of polarized dendrite morphology in pyramidal neurons remain poorly understood. Here, we report that the Angelman syndrome (AS) protein ubiquitin-protein ligase E3A (Ube3a) plays an important role in specifying the polarization of pyramidal neuron dendritic arbors in mice. shRNA-mediated downregulation of Ube3a selectively inhibited apical dendrite outgrowth and resulted in impaired dendrite polarity, which could be rescued by coexpressing mouse Ube3a isoform 2, but not isoform 1 or 3. Ube3a knockdown also disrupted the polarized distribution of the Golgi apparatus, a well established cellular mechanism for asymmetric dendritic growth in pyramidal neurons. Furthermore, downregulation of Ube3a completely blocked Reelin-induced rapid deployment of Golgi into dendrite. Consistently, we also observed selective inhibition of apical dendrite outgrowth in pyramidal neurons in a mouse model of AS. Overall, these results show that Ube3a is required for the specification of the apical dendrites and dendrite polarization in pyramidal neurons, and suggest a novel pathological mechanism for AS.
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Miao
authors.forename: Renchao
authors.initials: R
authors.lastname: Chen
authors.forename: Jiahao
authors.initials: J
authors.lastname: Ye
authors.forename: Guo-He
authors.initials: GH
authors.lastname: Tan
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Yong-hui
authors.initials: YH
authors.lastname: Jiang
authors.forename: Zhi-Qi
authors.initials: ZQ
authors.lastname: Xiong
mesh_terms: D017204:Angelman Syndrome / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016764:Cell Polarity / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism*; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism; D051379:Mice; D055495:Neurogenesis / Q000502:physiology; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism*; D034741:RNA, Small Interfering; D000091042:Reelin Protein; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D000091042:Reelin Protein; C502429:Ube3a protein, mouse; D044767:Ubiquitin-Protein Ligases; C000717128:Reln protein, mouse