HtrA1-dependent proteolysis of TGF-beta controls both neuronal maturation and developmental survival.
Cell Death Differ
; 15(9): 1408-16, 2008 Sep.
Article
in En
| MEDLINE
| ID: mdl-18551132
ABSTRACT
Transforming growth factor-beta (TGF-beta) signalling controls a number of cerebral functions and dysfunctions including synaptogenesis, amyloid-beta accumulation, apoptosis and excitotoxicity. Using cultured cortical neurons prepared from either wild type or transgenic mice overexpressing a TGF-beta-responsive luciferase reporter gene (SBE-Luc), we demonstrated a progressive loss of TGF-beta signalling during neuronal maturation and survival. Moreover, we showed that neurons exhibit increasing amounts of the serine protease HtrA1 (high temperature responsive antigen 1) and corresponding cleavage products during both in vitro neuronal maturation and brain development. In parallel of its ability to promote degradation of TGF-beta1, we demonstrated that blockage of the proteolytic activity of HtrA1 leads to a restoration of TGF-beta signalling, subsequent overexpression of the serpin type -1 plasminogen activator inhibitor (PAI-1) and neuronal death. Altogether, we propose that the balance between HtrA1 and TGF-beta could be one of the critical events controlling both neuronal maturation and developmental survival.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain
/
Serine Endopeptidases
/
Transforming Growth Factor beta1
/
Neurons
Limits:
Animals
Language:
En
Journal:
Cell Death Differ
Year:
2008
Document type:
Article
Affiliation country:
Francia