Format

Send to

Choose Destination
J Cell Sci. 2016 Oct 15;129(20):3792-3802. Epub 2016 Aug 26.

Prolyl endopeptidase is involved in the degradation of neural cell adhesion molecules in vitro.

Author information

1
Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu 50411, Estonia Kulli.Jaako@ut.ee.
2
Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig 04103, Germany.
3
Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu 50411, Estonia.
4
Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp B-2610, Belgium.
5
Interdisciplinary Research Centre KU Leuven-Kortrijk, Kortrijk B-8500, Belgium.

Abstract

Membrane-associated glycoprotein neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) play an important role in brain plasticity by regulating cell-cell interactions. Here, we demonstrate that the cytosolic serine protease prolyl endopeptidase (PREP) is able to regulate NCAM and PSA-NCAM. Using a SH-SY5Y neuroblastoma cell line with stable overexpression of PREP, we found a remarkable loss of PSA-NCAM, reduced levels of NCAM180 and NCAM140 protein species, and a significant increase in the NCAM immunoreactive band migrating at an apparent molecular weight of 120 kDa in PREP-overexpressing cells. Moreover, increased levels of NCAM fragments were found in the concentrated medium derived from PREP-overexpressing cells. PREP overexpression selectively induced an activation of matrix metalloproteinase-9 (MMP-9), which could be involved in the observed degradation of NCAM, as MMP-9 neutralization reduced the levels of NCAM fragments in cell culture medium. We propose that increased PREP levels promote epidermal growth factor receptor (EGFR) signaling, which in turn activates MMP-9. In conclusion, our findings provide evidence for newly-discovered roles for PREP in mechanisms regulating cellular plasticity through NCAM and PSA-NCAM.

KEYWORDS:

Metalloproteinase-9; Neural cell adhesion molecule; Neuronal plasticity; Prolyl endopeptidase

PMID:
27566163
DOI:
10.1242/jcs.181891
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center