Utilizing the peptidyl-prolyl cis-trans isomerase pin1 as a probe of its phosphorylated target proteins. Examples of binding to nuclear proteins in a human kidney cell line and to tau in Alzheimer's diseased brain.
The human parvulin Pin1 is a member of the peptidyl-prolyl cis-trans isomerase group of proteins, which modulate the assembly, folding, activity, and transport of essential cellular proteins. Pin1 is a mitotic regulator interacting with a range of proteins that are phosphorylated before cell division. In addition, an involvement of Pin1 in the tau-related neurodegenerative brain disorders has recently been shown. In this context, Pin1 becomes depleted from the nucleus in Alzheimer's disease (AD) neurons when it is redirected to the large amounts of hyperphosphorylated tau associated with the neurofibrillary tangles. This depletion from the nucleus may ultimately contribute to neuron cell death. Recently we have devised a novel methodology in which exogenous Pin1 is used as a TEM probe for its target proteins. Here we extend this methodology to provide further evidence that Pin1 binds at enhanced levels to mitotic nuclear proteins and to hyperphosphorylated tau in AD brain. We suggest that exogenous Pin1 labeling can be used to elucidate the phosphorylation status of its target proteins in general and could specifically provide important insights into the development of tau-related neurodegenerative brain disorders.
Thorpe
J R
JR
Electron Microscope and FACS Laboratory, School of Biological Sciences, University of Sussex, Brighton, United Kingdom. J.R.Thorpe@sussex.ac.uk
Morley
S J
SJ
Rulten
S L
SL
D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry / Q000379:methods; D007668:Kidney / Q000166:cytology; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D015335:Molecular Probes; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D015739:Nocodazole / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism*; D019696:Peptidylprolyl Isomerase / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D015335:Molecular Probes; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins; D016875:tau Proteins; D013912:Threonine; D012694:Serine; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; D015739:Nocodazole