Neuroscience Bulletin

, Volume 26, Issue 4, pp 338–344

A possible role of myristoylated alanine-rich C kinase substrate in endocytic pathway of Alzheimer’s disease

  • Rui Su (苏芮)
  • Zhen-Yun Han (韩振蕴)
  • Ji-Ping Fan (范吉平)
  • Yun-Ling Zhang (张允岭)
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DOI: 10.1007/s12264-010-0131-0

Cite this article as:
Su, R., Han, ZY., Fan, JP. et al. Neurosci. Bull. (2010) 26: 338. doi:10.1007/s12264-010-0131-0

Abstract

It is believed that amyloid-β peptide (Aβ) plays a central role in the pathogenesis of Alzheimer’s disease (AD). Thus, the process of amyloid precursor protein (APP) cleavage is a key event and has raised much attention in the field of AD research. It is proposed that APP, β- and γ-secretases are all located on the lipid raft, and the meeting of them is an indispensable step for Aβ generation. Endocytosis can lead to clustering of APP, β- and γ-secretases from separate smaller lipid rafts into a larger one. On the other hand, for myristoylated alanine-rich C kinase substrate (MARCKS), phosphorylation by protein kinase C (PKC) or interaction with Ca2+ can lead to its release from membrane into cytoplasm. This process induces the release of actins and phosphatidylinositol 4, 5-bisphosphate (PIP2), which are important factors for endocytosis. Thus, the present review proposes that MARCKS may be implicated in Aβ generation, by modulating free PIP2 level and actin movement, causing endocytosis.

Keywords

Alzheimer’s disease endocytosis myristoylated alanine-rich C kinase substrate lipid raft phosphatidylinositol 4, 5-bisphosphate actin cytoskeleton 

豆蔻酰化的富丙氨酸的蛋白激酶C 的底物在阿尔茨海默病胞吞过程中的作用

摘要

β淀粉样蛋白(amyloid β, Aβ)在阿尔茨海默病(Alzheimer’s disease, AD)的发病过程中的重要作用已为人熟知。 淀粉样前体蛋白(amyloid precursor protein, APP)的水解过程也因此成为AD研究的重点。 APP、 β-和γ-分泌酶都位 于脂筏上, 三者的相遇是产生Aβ 的必要步骤, 而胞吞作用则能使分布在微小脂筏上的APP、 β-和γ-分泌酶集中 到较大的脂筏上。 另一方面, 豆蔻酰化的富丙氨酸的蛋白激酶C的底物(myristoylated alanine-rich C kinase substrate, MARCKS)被蛋白激酶C磷酸化或与钙离子作用后, 会离开细胞膜进入细胞质, 进而引起在胞吞作用中起重要作用 的肌动蛋白和4, 5-二磷酸肌醇(PIP2)的释放。 因此, 本文提出假说, 认为MARCKS通过调节自由态PIP2 的水平和 肌动蛋白的运动, 引发胞吞作用, 进而在Aβ 的产生过程中起重要作用。

关键词

阿尔茨海默病 胞吞 豆蔻酰化的富丙氨酸的蛋白激酶C 的底物 脂筏 4, 5-二磷酸肌醇 肌动蛋白 细胞骨架 

Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Rui Su (苏芮)
    • 1
  • Zhen-Yun Han (韩振蕴)
    • 2
  • Ji-Ping Fan (范吉平)
    • 1
  • Yun-Ling Zhang (张允岭)
    • 2
  1. 1.China Academy of Chinese Medical SciencesBeijingChina
  2. 2.Beijing University of Traditional Chinese Medicine subsidiary Dongfang HospitalBeijingChina

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