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

Author:

Jaako Külli1ORCID,Waniek Alexander2,Parik Keiti1,Klimaviciusa Linda1ORCID,Aonurm-Helm Anu1,Noortoots Aveli1,Anier Kaili1,Van Elzen Roos3,Gérard Melanie4,Lambeir Anne-Marie3,Roßner Steffen2,Morawski Markus2,Zharkovsky Alexander1

Affiliation:

1. Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 9, Ravila Str. 50411, Tartu, Estonia

2. University of Leipzig, Paul Flechsig Institute for Brain Research, Liebigstr. 19. 04103, Leipzig, Germany

3. Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, B-2610, Antwerp, Belgium

4. Interdisciplinary Research Centre KU Leuven-Kortrijk, B-8500, Kortrijk, Belgium

Abstract

Neural cell adhesion molecule (NCAM), a membrane-associated glycoprotein and its polysialylated form (PSA-NCAM) play an important role in brain plasticity via regulating cell-cell interactions. Here, we demonstrate that the cytosolic serine protease prolyl endopeptidase (PREP) is able to regulate NCAM and PSA-NCAM. Using SH-SY5Y neuroblastoma cell line with stable overexpression of PREP we found a remarkable loss in PSA-NCAM and reduced levels of NCAM 180 kDa and NCAM 140 kDa 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 in the concentrated medium derived from PREP-overexpressing cells were found. 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 (EGF)-receptor signaling, which in turn activates MMP-9. In conclusion, our findings provide evidence for the novel roles for PREP in mechanisms regulating cellular plasticity via NCAM and PSA-NCAM.

Funder

EU grant NEUROPRO

Estonian Science Foundation

Estonian Science Council Grant

Deutsche Forschungsgemeinschaft within the PP 1608

GRK 1097 INTERNEURO

Alzheimer Forschungsinitiativee.V.

European Union and the Federal State of Saxony Funding

UAntwerp special research fund grant

Sächsische Aufbaubank (SAB) | European Social Fund

Publisher

The Company of Biologists

Subject

Cell Biology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3