Pin1 allows for differential Tau dephosphorylation in neuronal cells.
Neurofibrillary degeneration is likely to be related to abnormal Tau phosphorylation and aggregation. Among abnormal Tau phosphorylation sites, pThr231 is of particular interest since it is associated with early stages of Alzheimer's disease and is a binding site of Pin1, a peptidyl-prolyl cis/trans isomerase mainly involved in cell cycle regulation. In the present work, Pin1 level was found strongly increased during neuronal differentiation and tightly correlated with Tau dephosphorylation at Thr231. Likewise, we showed in cellular model that Pin1 allowed for specific Tau dephosphorylation at Thr231, whereas other phosphorylation sites were unchanged. Moreover, cells displaying Tau phosphorylation at Thr231 did not show any Pin1 nuclear depletion. Altogether, these data indicate that Pin1 has key function(s) in neuron and is at least involved in the regulation of Tau phosphorylation at relevant sites. Hence, Pin1 dysfunction, unlikely by nuclear depletion, may have critical consequences on Tau pathological aggregation and neuronal death.
Hamdane
Malika
M
Inserm, U815, Institut de Médecine Prédictive et Recherche Thérapeutique, F-59045 Lille, France.
Dourlen
Pierre
P
Bretteville
Alexis
A
Sambo
Anne-Véronique
AV
Ferreira
Stéphanie
S
Ando
Kunie
K
Kerdraon
Olivier
O
Bégard
Séverine
S
Geay
Linda
L
Lippens
Guy
G
Sergeant
Nicolas
N
Delacourte
André
A
Maurage
Claude-Alain
CA
Galas
Marie-Christine
MC
Buée
Luc
L
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D013912:Threonine / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D016875:tau Proteins; D013912:Threonine; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase