14-3-3 isoforms in lipid rafts: the role in neurodegenerative diseases

Members of the 14-3-3 protein family are involved in the protein
aggregates that accumulate in specific areas of the brain in a number
of neurodegenerative disorders including Alzheimer’s, Creutzfeldt–
Jakob, Parkinson’s and polyglutamine-repeat diseases, such as
Huntington’s. Although the proteins are specific to each disease, the
common feature now emerging is the interaction of isoforms of 14-
3-3 with all of these. Many of these are processed or misfolded at
lipid rafts. Interactions with 14-3-3 are mainly regulated by
phosphorylation of the target protein. We and others have also
shown that phosphorylation of specific isoforms of 14-3-3 (on
Ser185 or Ser/Thr233) itself can negatively regulate interactions in
vivo. Of the seven mammalian isoforms of 14-3-3, five are
expressed to a high extent in brain and two of these are
phosphorylated to a high level on Ser185. We have shown
association of 14-3-3 isoforms with lipid rafts and are verifying
the presence of the phospho-forms of 14-3-3.