Metalloprotease meprin β is activated by transmembrane serine protease matriptase-2 at the cell surface thereby enhancing APP shedding

2015 ◽  
Vol 470 (1) ◽  
pp. 91-103 ◽  
Author(s):  
Felix Jäckle ◽  
Frederike Schmidt ◽  
Rielana Wichert ◽  
Philipp Arnold ◽  
Johannes Prox ◽  
...  
Keyword(s):  
Cell Surface ◽  
Serine Protease ◽  
Transmembrane Proteins ◽  
Mechanistic Insight ◽  
Transmembrane Serine Protease ◽  
Proenzyme Activation

Metalloprotease meprin β is a sheddase of transmembrane proteins. We identified serine protease matriptase-2 (MT2) as a specific activator of meprin β at the cell surface. This provides mechanistic insight for the regulation of meprin β activity and demonstrates clear differences in proenzyme activation.

scholarly journals Aerosolized type II transmembrane serine protease 2 inhibitor to combat COVID-19: a proposal

2021 ◽  
Vol 8 (12) ◽  
pp. 1996
Author(s):  
Chandan Raybarman ◽  
Surajit Bhattacharjee
Keyword(s):  
Cell Surface ◽  
Serine Protease ◽  
Viral Entry ◽  
Type Ii ◽  
Cellular Entry ◽  
Transmembrane Serine Protease

Type II transmembrane serine protease (TMPRSS2) is expressed at the cell surface with COVID-19 infection. And COVID-19 infection misuse TMPRSS2 to advance their spread, making this protease potential focuses for intervention in COVID-19 infection. TMPRSS2 blocker may be the appropriate option to arrest cellular entry of COVID-19 by deregulating spike priming. Therefore a trial may be intended to watch the adequacy of aerosolized spraying of TMPRSS2 inhibitors to break the viral entry to the objective cells that empower to break the COVID-19 transmission. Targeting TMPRSS2 through aerosolized TMPRSS2 inhibitor is important to examine a possibly viable remedial technique in the treatment of COVID-19.

scholarly journals Middle East Respiratory Syndrome Coronavirus Infection Mediated by the Transmembrane Serine Protease TMPRSS2

2013 ◽  
Vol 87 (23) ◽  
pp. 12552-12561 ◽  
Author(s):  
Kazuya Shirato ◽  
Miyuki Kawase ◽  
Shutoku Matsuyama
Keyword(s):  
Middle East ◽  
Cell Surface ◽  
Serine Protease ◽  
Virus Entry ◽  
Cathepsin L ◽  
Vero Cells ◽  
Middle East Respiratory Syndrome ◽  
Simultaneous Treatment ◽  
Virus Growth ◽  
Transmembrane Serine Protease

The Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes host proteases for virus entry into lung cells. In the current study, Vero cells constitutively expressing type II transmembrane serine protease (Vero-TMPRSS2 cells) showed larger syncytia at 18 h after infection with MERS-CoV than after infection with other coronaviruses. Furthermore, the susceptibility of Vero-TMPRSS2 cells to MERS-CoV was 100-fold higher than that of non-TMPRSS2-expressing parental Vero cells. The serine protease inhibitor camostat, which inhibits TMPRSS2 activity, completely blocked syncytium formation but only partially blocked virus entry into Vero-TMPRSS2 cells. Importantly, the coronavirus is thought to enter cells via two distinct pathways, one mediated by TMPRSS2 at the cell surface and the other mediated by cathepsin L in the endosome. Simultaneous treatment with inhibitors of cathepsin L and TMPRSS2 completely blocked virus entry into Vero-TMPRSS2 cells, indicating that MERS-CoV employs both the cell surface and the endosomal pathway to infect Vero-TMPRSS2 cells. In contrast, a single camostat treatment suppressed MERS-CoV entry into human bronchial submucosal gland-derived Calu-3 cells by 10-fold and virus growth by 270-fold, although treatment with both camostat and (23,25)-trans-epoxysuccinyl-l-leucylamindo-3-methylbutane ethyl ester, a cathepsin inhibitor, or treatment with leupeptin, an inhibitor of cysteine, serine, and threonine peptidases, was no more efficacious than treatment with camostat alone. Further, these inhibitors were not efficacious against MERS-CoV infection of MRC-5 and WI-38 cells, which were derived from lung, but these characters differed from those of mature pneumocytes. These results suggest that a single treatment with camostat is sufficient to block MERS-CoV entry into a well-differentiated lung-derived cell line.

scholarly journals Phenotypic Analysis of Mice Lacking the Tmprss2-Encoded Protease

2006 ◽  
Vol 26 (3) ◽  
pp. 965-975 ◽  
Author(s):  
Tom S. Kim ◽  
Cynthia Heinlein ◽  
Robert C. Hackman ◽  
Peter S. Nelson
Keyword(s):  
Serine Protease ◽  
Serine Proteases ◽  
Biological Activities ◽  
Type Ii ◽  
Phenotypic Analysis ◽  
Normal Prostate ◽  
Prostate Hyperplasia ◽  
Transmembrane Serine Protease

ABSTRACT Tmprss2 encodes an androgen-regulated type II transmembrane serine protease (TTSP) expressed highly in normal prostate epithelium and has been implicated in prostate carcinogenesis. Although in vitro studies suggest protease-activated receptor 2 may be a substrate for TMPRSS2, the in vivo biological activities of TMPRSS2 remain unknown. We generated Tmprss2 −/− mice by disrupting the serine protease domain through homologous recombination. Compared to wild-type littermates, Tmprss2 −/− mice developed normally, survived to adulthood with no differences in protein levels of prostatic secretions, and exhibited no discernible abnormalities in organ histology or function. Loss of TMPRSS2 serine protease activity did not influence fertility, reduce survival, result in prostate hyperplasia or carcinoma, or alter prostatic luminal epithelial cell regrowth following castration and androgen replacement. Lack of an observable phenotype in Tmprss2 −/− mice was not due to transcriptional compensation by closely related Tmprss2 homologs. We conclude that the lack of a discernible phenotype in Tmprss2 −/− mice suggests functional redundancy involving one or more of the type II transmembrane serine protease family members or other serine proteases. Alternatively, TMPRSS2 may contribute a specialized but nonvital function that is apparent only in the context of stress, disease, or other systemic perturbation.

scholarly journals Magnesium Treatment on Methylation Changes of Transmembrane Serine Protease 2 (TMPRSS2)

Nutrition ◽  
2021 ◽  
pp. 111340
Author(s):  
Lei Fan ◽  
Xiangzhu Zhu ◽  
Yinan Zheng ◽  
Wei Zhang ◽  
Douglas L Seidner ◽  
...  
Keyword(s):  
Serine Protease ◽  
Transmembrane Serine Protease ◽  
Magnesium Treatment

Intracellular traffic of the ecto-nucleotide pyrophosphatase/phosphodiesterase NPP3 to the apical plasma membrane of MDCK and Caco-2 cells: apical targeting occurs in the absence of N-glycosylation

2000 ◽  
Vol 113 (23) ◽  
pp. 4193-4202 ◽  
Author(s):  
N.R. Meerson ◽  
V. Bello ◽  
J.L. Delaunay ◽  
T.A. Slimane ◽  
D. Delautier ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mdck Cells ◽  
Transmembrane Proteins ◽  
Cell Types ◽  
Apical Plasma Membrane ◽  
Apical Surface ◽  
Intracellular Traffic ◽  
Transmembrane Glycoprotein ◽  
Direct Demonstration ◽  
Targeting Signal

Glycosylation was considered the major signal candidate for apical targeting of transmembrane proteins in polarized epithelial cells. However, direct demonstration of the role of glycosylation has proved difficult because non-glycosylated apical transmembrane proteins usually do not reach the cell surface. Here we were able to follow the targeting of the apical transmembrane glycoprotein NPP3 both when glycosylated and non-glycosylated. Transfected in polarized MDCK and Caco-2 cells, NPP3 was exclusively expressed at the apical membrane. The transport kinetics of the protein to the cell surface were studied after metabolic (35)S-labeling and surface immunoprecipitation. The newly synthesized protein was mainly targeted directly to the apical surface in MDCK cells, whereas 50% transited through the basolateral surface in Caco-2 cells. In both cell types, the basolaterally targeted pool was effectively transcytosed to the apical surface. In the presence of tunicamycin, NPP3 was not N-glycosylated. The non-glycosylated protein was partially retained intracellularly but the fraction that reached the cell surface was nevertheless predominantly targeted apically. However, transcytosis of the non-glycosylated protein was partially impaired in MDCK cells. These results provide direct evidence that glycosylation cannot be considered an apical targeting signal for NPP3, although glycosylation is necessary for correct trafficking of the protein to the cell surface.

The Type II Transmembrane Serine Protease, Matriptase-2: Possible Links to Cancer?

2010 ◽  
Vol 10 (1) ◽  
pp. 64-69 ◽  
Author(s):  
Andrew Sanders ◽  
Siobhan Webb ◽  
Christian Parr ◽  
Malcolm Mason ◽  
Wen Jiang
Keyword(s):  
Serine Protease ◽  
Type Ii ◽  
Transmembrane Serine Protease
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