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Title: The Angelman Syndrome Protein Ube3a Is Required for Polarized Dendrite Morphogenesis in Pyramidal Neurons
Author: Miao, S ; Chen, RC ; Ye, JH ; Tan, GH ; Li, S ; Zhang, J ; Jiang, YH ; Xiong, ZQ
Source: JOURNAL OF NEUROSCIENCE
Issued Date: 2013
Volume: 33, Issue:1, Pages:327-333
Keyword: UBIQUITIN LIGASE ; E6-ASSOCIATED PROTEIN ; CEREBRAL-CORTEX ; GENE-TRANSFER ; MIGRATION ; SYNAPSE ; ELECTROPORATION ; DEGRADATION ; ORIENTATION ; NEOCORTEX
Subject: Neurosciences & Neurology
Corresponding Author: Xiong, ZQ (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,xiongzhiqi@ion.ac.cn
English 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.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/2529
Appears in Collections:神经所(总)_期刊论文

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Miao, S; Chen, RC; Ye, JH; Tan, GH; Li, S; Zhang, J; Jiang, YH; Xiong, ZQ.The Angelman Syndrome Protein Ube3a Is Required for Polarized Dendrite Morphogenesis in Pyramidal Neurons,JOURNAL OF NEUROSCIENCE,2013,33(1):327-333
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