ApoE3 binding to tau tandem repeat I is abolished by tau serine262 phosphorylation.
The risk of Alzheimer's disease is determined, in part, by inheritance of specific alleles of ApoE. Isoform specific interactions of ApoE have been shown with the microtubule-associated protein tau, which forms the neurofibrillary tangle in this disease. Synthetic peptides representing each of the four microtubule-binding domains of tau more avidly bind ApoE3 than ApoE4. Phosphorylation of serine262 in domain I of tau decreases tau binding to microtubules and also abolishes binding by ApoE3. Understanding the molecular mechanisms of the high avidity, isoform-specific interactions of ApoE with tau may help in developing approaches for disease intervention.
Huang
D Y
DY
Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710, USA.
Weisgraber
K H
KH
Goedert
M
M
Saunders
A M
AM
Roses
A D
AD
Strittmatter
W J
WJ
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D012694:Serine / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism* / Q000648:ultrastructure
D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D016875:tau Proteins; D012694:Serine