title: A possible role of myristoylated alanine-rich C kinase substrate in endocytic pathway of Alzheimer's disease.
abstract: It is believed that amyloid-beta peptide (Abeta) 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, beta- and gamma-secretases are all located on the lipid raft, and the meeting of them is an indispensable step for Abeta generation. Endocytosis can lead to clustering of APP, beta- and gamma-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 Ca(2+) 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 Abeta generation, by modulating free PIP2 level and actin movement, causing endocytosis.
authors.affiliation: China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Su
authors.forename: Zhen-Yun
authors.initials: ZY
authors.lastname: Han
authors.forename: Ji-Ping
authors.initials: JP
authors.lastname: Fan
authors.forename: Yun-Ling
authors.initials: YL
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D000076250:Myristoylated Alanine-Rich C Kinase Substrate
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; D008565:Membrane Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate