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Title: Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity
Author: Chen, YM ; Wang, QJ ; Hu, HS ; Yu, PC ; Zhu, J ; Drewes, G ; Piwnica-Worms, H ; Luo, ZG
Source: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Issued Date: 2006
Volume: 103, Issue:22, Pages:8534-8539
Keyword: polarity complex ; partition-defective protein 1b ; axon specification ; PROTEIN-KINASE ; CELL-POLARITY ; TAU-PROTEIN ; PHOSPHORYLATION ; ESTABLISHMENT ; GSK-3-BETA ; PAR-1 ; APKC ; AXON ; SPECIFICATION
Subject: Science & Technology - Other Topics
Corresponding Author: Luo, ZG (reprint author), Chinese Acad Sci, Inst Neurosci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China,zgluo@ion.ac.cn
English Abstract: 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.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1821
Appears in Collections:神经所(总)_期刊论文

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Chen, YM; Wang, QJ; Hu, HS; Yu, PC; Zhu, J; Drewes, G; Piwnica-Worms, H; Luo, ZG.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,2006,103(22):8534-8539
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