Prolidase enzyme is required for extracellular matrix integrity and impacts on postnatal cerebellar cortex development.


Journal

The Journal of comparative neurology
ISSN: 1096-9861
Titre abrégé: J Comp Neurol
Pays: United States
ID NLM: 0406041

Informations de publication

Date de publication:
01 01 2020
Historique:
received: 23 01 2019
revised: 11 06 2019
accepted: 20 06 2019
pubmed: 28 6 2019
medline: 2 7 2021
entrez: 28 6 2019
Statut: ppublish

Résumé

The extracellular matrix is essential for brain development, lamination, and synaptogenesis. In particular, the basement membrane below the pial meninx (pBM) is required for correct cortical development. The last step in the catabolism of the most abundant protein in pBM, collagen Type IV, requires prolidase, an exopeptidase cleaving the imidodipeptides containing pro or hyp at the C-terminal end. Mutations impairing prolidase activity lead in humans to the rare disease prolidase deficiency characterized by severe skin ulcers and mental impairment. Thus, the dark-like (dal) mouse, in which the prolidase is knocked-out, was used to investigate whether the deficiency of prolidase affects the neuronal maturation during development of a brain cortex area. Focusing on the cerebellar cortex, thinner collagen fibers and disorganized pBM were found. Aberrant cortical granule cell proliferation and migration occurred, associated to defects in brain lamination, and in particular in maturation of Purkinje neurons and formation of synaptic contacts. This study deeply elucidates a link between prolidase activity and neuronal maturation shedding new light on the molecular basis of functional aspects in the prolidase deficiency.

Identifiants

pubmed: 31246278
doi: 10.1002/cne.24735
doi:

Substances chimiques

Dipeptidases EC 3.4.13.-
proline dipeptidase EC 3.4.13.9

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

61-80

Informations de copyright

© 2019 Wiley Periodicals, Inc.

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Auteurs

Violetta Insolia (V)

Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.

Erica C Priori (EC)

Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.

Caterina Gasperini (C)

Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.

Federica Coppa (F)

Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.

Marco Cocchia (M)

Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.

Erika Iervasi (E)

Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.

Beatrice Ferrari (B)

Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.

Roberta Besio (R)

Department of Molecular Medicine, Biochemistry Unit, University of Pavia, Pavia, Italy.

Silvia Maruelli (S)

Department of Molecular Medicine, Biochemistry Unit, University of Pavia, Pavia, Italy.

Graziella Bernocchi (G)

Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.

Antonella Forlino (A)

Department of Molecular Medicine, Biochemistry Unit, University of Pavia, Pavia, Italy.

Maria G Bottone (MG)

Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.

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