Binding of alpha-fodrin to gamma-tubulin accounts for its role in the inhibition of microtubule nucleation

FEBS Letters

article

Jamuna S. Sreeja¹  Rohith Kumar Nellikka¹  Rince John¹  Krishnankutty C. Sivakumar²  Easwaran Sreekumar¹  Suparna Sengupta¹ 

[1] Cancer Research Programme, Rajiv Gandhi Centre for Biotechnology;Distributed Information Sub-Centre, Rajiv Gandhi Centre for Biotechnology

关键词: fodrin;    gamma-tubulin;    GRIP2 motif;    microtubule;    nucleation;   

DOI  :  10.1002/1873-3468.13425

来源: John Wiley & Sons Ltd.

【 摘 要 】

Apolipoprotein E (APOE) genotype determines Alzheimer’s disease (AD) susceptibility, with the APOE e4 allele being an established risk factor for lateonset AD. The ApoE lipidation status has been reported to impact amyloidbeta (Ab) peptide metabolism. The details of how lipidation affects ApoE behavior remain to be elucidated. In this study, we prepared lipid-free and lipid-bound ApoE particles, mimicking the high-density lipoprotein particles found in vivo, for all three isoforms (ApoE2, ApoE3, and ApoE4) and biophysically characterized them. We find that lipid-free ApoE in solution has the tendency to aggregate in vitro in an isoform-dependent manner under near-physiological conditions and that aggregation is impeded by lipidation of ApoE.

【 授权许可】

Unknown