Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity
文献类型:期刊论文
作者 | Chen, YM ; Wang, QJ ; Hu, HS ; Yu, PC ; Zhu, J ; Drewes, G ; Piwnica-Worms, H ; Luo, ZG |
刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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出版日期 | 2006 |
卷号 | 103期号:22页码:8534-8539 |
关键词 | polarity complex partition-defective protein 1b axon specification PROTEIN-KINASE CELL-POLARITY TAU-PROTEIN PHOSPHORYLATION ESTABLISHMENT GSK-3-BETA PAR-1 APKC AXON SPECIFICATION |
ISSN号 | 0027-8424 |
通讯作者 | Luo, ZG (reprint author), Chinese Acad Sci, Inst Neurosci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China,zgluo@ion.ac.cn |
英文摘要 | The PAR-3/PAR-6/atypical PKC (aPKC) complex is required for axon-dendrite specification of hippocampal neurons. However, the downstream effectors of this complex are not well defined. In this article, we report a role for microtubule affinity-regulating kinase (MARK)/PAR-1 in axon-dendrite specification. Knocking down MARK2 expression with small interfering RNAs induced formation of multiple axon-like neurites and promoted axon outgrowth. Ectopic expression of MARK2 caused phosphorylation of tau (S262) and led to loss of axons, and this phenotype was rescued by expression of PAR-3, PAR-6, and aPKC. In contrast, the polarity defects caused by an MARK2 mutant (T595A), which is not responsive to aPKC, were not rescued by the PAR-3/PAR-6/aPKC complex. Moreover, polarity was abrogated in neurons overexpressing a mutant of MARK2 with a deleted kinase domain but an intact aPKC-binding domain. Finally, suppression of MARK2 rescued the polarity defects induced by a dominant-negative aPKC mutant. These results suggest that MARK2 is involved in neuronal polarization and functions downstream of the PAR-3/PAR-6/aPKC complex. We propose that aPKC in complex with PAR-3/PAR-6 negatively regulates MARK(s), which in turn causes dephosphorylation of microtubule-associated proteins, such as tau, leading to the assembly of microtubules and elongation of axons. |
学科主题 | Science & Technology - Other Topics |
收录类别 | SCI |
语种 | 英语 |
公开日期 | 2012-07-23 |
源URL | [http://ir.sibs.ac.cn/handle/331001/1821] ![]() |
专题 | 上海神经科学研究所_神经所(总) |
推荐引用方式 GB/T 7714 | Chen, YM,Wang, QJ,Hu, HS,et al. Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2006,103(22):8534-8539. |
APA | Chen, YM.,Wang, QJ.,Hu, HS.,Yu, PC.,Zhu, J.,...&Luo, ZG.(2006).Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,103(22),8534-8539. |
MLA | Chen, YM,et al."Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 103.22(2006):8534-8539. |
入库方式: OAI收割
来源:上海神经科学研究所
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