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The Prolyl Isomerase Pin1 Stabilizes NeuroD During Differentiation of Mechanoreceptors

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Specialty Cell Biology
Date 2023 Oct 4
PMID 37791075
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Abstract

The peptidyl prolyl isomerase Pin1 plays vital roles in diverse cellular processes and pathological conditions. NeuroD is a differentiation and survival factor for a subset of neurons and pancreatic endocrine cells. Although multiple phosphorylation events are known to be crucial for NeuroD function, their mechanisms remain elusive. In this study, we demonstrate that zebrafish embryos deficient in Pin1 displayed phenotypes resembling those associated with NeuroD depletion, characterized by defects in formation of mechanosensory hair cells. Furthermore, zebrafish Pin1 interacts with NeuroD in a phosphorylation-dependent manner. In Pin1-deficient cell lines, NeuroD is rapidly degraded. However, the protein stability of NeuroD is restored upon overexpression of Pin1. These findings suggest that Pin1 functionally regulates NeuroD protein levels by post-phosphorylation isomerization during neuronal specification.

References
1.
Mantovani F, Piazza S, Gostissa M, Strano S, Zacchi P, Mantovani R . Pin1 links the activities of c-Abl and p300 in regulating p73 function. Mol Cell. 2004; 14(5):625-36. DOI: 10.1016/j.molcel.2004.05.007. View

2.
Miyata T, Maeda T, Lee J . NeuroD is required for differentiation of the granule cells in the cerebellum and hippocampus. Genes Dev. 1999; 13(13):1647-52. PMC: 316850. DOI: 10.1101/gad.13.13.1647. View

3.
Lu K, Zhou X . The prolyl isomerase PIN1: a pivotal new twist in phosphorylation signalling and disease. Nat Rev Mol Cell Biol. 2007; 8(11):904-16. DOI: 10.1038/nrm2261. View

4.
Oberst A, Rossi M, Salomoni P, Pandolfi P, Oren M, Melino G . Regulation of the p73 protein stability and degradation. Biochem Biophys Res Commun. 2005; 331(3):707-12. DOI: 10.1016/j.bbrc.2005.03.158. View

5.
Kimmel C, Ballard W, Kimmel S, Ullmann B, Schilling T . Stages of embryonic development of the zebrafish. Dev Dyn. 1995; 203(3):253-310. DOI: 10.1002/aja.1002030302. View