Tau pathology modulates Pin1 post-translational modifications and may be relevant as biomarker.
Kunie Ando
(1, 2)
,
Pierre Dourlen
(1, 2)
,
Anne-Véronique Sambo
(1, 2)
,
Alexis Bretteville
(1, 2)
,
Karim Bélarbi
(1, 2)
,
Valérie Vingtdeux
(1, 2)
,
Sabiha Eddarkaoui
(1, 2)
,
Hervé Drobecq
(2, 3)
,
Antoine Ghestem
(1, 2)
,
Séverine Bégard
(1, 2)
,
Emmanuelle Demey-Thomas
(4)
,
Patricia Melnyk
(2, 3)
,
Caroline Smet
(2, 5)
,
Guy Lippens
(2, 5)
,
Claude-Alain Maurage
(1, 2)
,
Marie-Laure Caillet-Boudin
(1, 2)
,
Yann Verdier
(4)
,
Joelle Vinh
(4)
,
Isabelle Landrieu
(2, 5)
,
Marie-Christine Galas
(1, 2)
,
David Blum
(1, 2)
,
Malika Hamdane
(1, 2)
,
Nicolas Sergeant
(1, 2)
,
Luc Buée
(1, 2)
1
JPArc -
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837
2 Université Lille Nord de France (COMUE)
3 IBLI - Institut de biologie de Lille - IBL
4 SMBP - Spectrométrie de Masse Biologique et Protéomique (USR3149 / FRE2032)
5 UGSF - Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
2 Université Lille Nord de France (COMUE)
3 IBLI - Institut de biologie de Lille - IBL
4 SMBP - Spectrométrie de Masse Biologique et Protéomique (USR3149 / FRE2032)
5 UGSF - Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
Antoine Ghestem
- Fonction : Auteur
- PersonId : 757089
- ORCID : 0000-0003-4864-609X
Patricia Melnyk
- Fonction : Auteur
- PersonId : 172378
- IdHAL : patricia-melnyk
- ORCID : 0000-0002-9555-3446
- IdRef : 120185156
Guy Lippens
- Fonction : Auteur
- PersonId : 1152294
- IdHAL : guy-lippens
- ORCID : 0000-0002-8236-0901
- IdRef : 061529613
Yann Verdier
- Fonction : Auteur
- PersonId : 16542
- IdHAL : yann-verdier
- ORCID : 0000-0002-3319-0053
Joelle Vinh
- Fonction : Auteur
- PersonId : 15430
- IdHAL : joellevinh
- ORCID : 0000-0001-7184-2668
- IdRef : 14488366X
Isabelle Landrieu
- Fonction : Auteur
- PersonId : 739391
- IdHAL : isabelle-landrieu
- ORCID : 0000-0002-4883-2637
- IdRef : 076929647
David Blum
- Fonction : Auteur
- PersonId : 181449
- IdHAL : david-blum
- ORCID : 0000-0001-5691-431X
- IdRef : 153625716
Luc Buée
- Fonction : Auteur
- PersonId : 173203
- IdHAL : luc-buee
- ORCID : 0000-0002-6261-4230
- IdRef : 075014068
Résumé
A prerequisite to dephosphorylation at Ser-Pro or Thr-Pro motifs is the isomerization of the imidic peptide bond preceding the proline. The peptidyl-prolyl cis/trans isomerase named Pin1 catalyzes this mechanism. Through isomerization, Pin1 regulates the function of a growing number of targets including the microtubule-associated tau protein and is supposed to be deregulated Alzheimer's disease (AD). Using proteomics, we showed that Pin1 is posttranslationally modified on more than 5 residues, comprising phosphorylation, N-acetylation, and oxidation. Although Pin1 expression remained constant, Pin1 posttranslational two-dimensional pattern was modified by tau overexpression in a tau-inducible neuroblastoma cell line, in our THY-Tau22 mouse model of tauopathy as well as in AD. Interestingly, in all of these systems, Pin1 modifications were very similar. In AD brain tissue when compared with control, Pin1 is hyperphosphorylated at serine 16 and found in the most insoluble hyperphosphorylated tau fraction of AD brain tissue. Furthermore, in all tau pathology conditions, acetylation of Pin1 may also contribute to the differences observed. In conclusion, Pin1 displays several posttranslational modifications, which are specific in tauopathies and may be useful as biomarker.