Kinesin-1 inhibits the aggregation of amyloid-β peptide as detected by fluorescence cross-correlation spectroscopy

Yanpeng Zheng; Shijun Tian; Xianglei Peng; Jingfa Yang; Yuanhui Fu; Yueying Jiao; Jiang Zhao; Jinsheng He; Tao Hong

doi:10.1002/1873-3468.12137

Kinesin-1 inhibits the aggregation of amyloid-β peptide as detected by fluorescence cross-correlation spectroscopy

FEBS Lett. 2016 Apr;590(7):1028-37. doi: 10.1002/1873-3468.12137. Epub 2016 Mar 29.

Authors

Yanpeng Zheng¹, Shijun Tian¹, Xianglei Peng¹, Jingfa Yang², Yuanhui Fu¹, Yueying Jiao¹, Jiang Zhao², Jinsheng He¹, Tao Hong^{1

3}

Affiliations

¹ College of Life Sciences and Bioengineering, Beijing Jiaotong University, China.
² Beijing National Laboratory for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.
³ Institute for Viral Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing, China.

PMID: 26991731
DOI: 10.1002/1873-3468.12137

Abstract

Although the exact etiology and pathogenesis of Alzheimer's disease (AD) are still unclear, amyloid-β (Aβ) generated by the proteolytic processing of amyloid-β precursor protein (APP) aggregate to form toxic amyloid species. Kinesin-1 is the first identified ATP-dependent axonal transport motor protein that has been proven to affect Aβ generation and deposition. In this paper, we applied dual-color fluorescence cross-correlation spectroscopy (DC-FCCS) to investigate the direct interaction of Aβ with kinesin-1 at the single-molecule fluorescence level in vitro. The results showed that two kinds of enhanced green fluorescent protein (EGFP)-tagged kinesin light-chain subunits of kinesin-1(KLCs), KLC-E and E-KLC inhibited the aggregation of Aβ over a period of time, providing additional insight into the mechanism of axonal transport deficits in AD.

Keywords: Alzheimer's disease; amyloid β; fluorescence cross-correlation spectroscopy; kinesin-1.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Algorithms
Amino Acid Substitution
Amyloid beta-Peptides / antagonists & inhibitors*
Amyloid beta-Peptides / chemistry
Amyloid beta-Peptides / genetics
Amyloid beta-Peptides / metabolism
Animals
Apolipoproteins E / genetics
Apolipoproteins E / metabolism
Cell Line
Fluorescent Dyes / chemistry
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Humans
Kinesins / chemistry
Kinesins / genetics
Kinesins / metabolism*
Kinetics
Mutation
Peptide Fragments / antagonists & inhibitors*
Peptide Fragments / chemistry
Peptide Fragments / genetics
Peptide Fragments / metabolism
Protein Aggregation, Pathological / metabolism
Protein Aggregation, Pathological / prevention & control*
Protein Interaction Domains and Motifs
Protein Subunits / chemistry
Protein Subunits / genetics
Protein Subunits / metabolism
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / metabolism
Spectrometry, Fluorescence

Substances

Amyloid beta-Peptides
Apolipoproteins E
Fluorescent Dyes
KIF5B protein, human
Peptide Fragments
Protein Subunits
Recombinant Fusion Proteins
amyloid beta-protein (1-42)
enhanced green fluorescent protein
Green Fluorescent Proteins
Kinesins