scholarly journals Activation-coupled membrane-type 1 matrix metalloproteinase membrane trafficking

2007 ◽  
Vol 407 (2) ◽  
pp. 171-177 ◽  
Author(s):  
Yi I. Wu ◽  
Hidayatullah G. Munshi ◽  
Scott J. Snipas ◽  
Guy S. Salvesen ◽  
Rafael Fridman ◽  
...  
Keyword(s):  
Cell Surface ◽  
Matrix Metalloproteinase ◽  
Cancer Progression ◽  
Membrane Trafficking ◽  
Stable Complex ◽  
Zymogen Activation ◽  
Critical Function ◽  
Membrane Type ◽  
Collagen Invasion

The transmembrane collagenase MT1-MMP (membrane-type 1 matrix metalloproteinase), also known as MMP-14, has a critical function both in normal development and in cancer progression, and is subject to extensive controls at the post-translational level which affect proteinase activity. As zymogen activation is crucial for MT1-MMP activity, an α1-PI (α1-proteinase inhibitor)-based inhibitor was designed by incorporating the MT1-MMP propeptide cleavage sequence into the α1-PI reactive-site loop (designated α1-PIMT1) and this was compared with wild-type α1-PI (α1-PIWT) and the furin inhibitory mutant α1-PIPDX. α1-PIMT1 formed an SDS-stable complex with furin and inhibited proMT1-MMP activation. A consequence of the loss of MT1-MMP activity was the activation of proMMP-2 and the inhibition of MT1-MMP-mediated collagen invasion. α1-PIMT1 expression also resulted in the intracellular accumulation of a glycosylated species of proMT1-MMP that was retained in the perinuclear region, leading to significantly decreased cell-surface accumulation of proMT1-MMP. These observations suggest that both the subcellular localization and the activity of MT1-MMP are regulated in a coordinated fashion, such that proMT1-MMP is retained intracellularly until activation of its zymogen, then proMT1-MMP traffics to the cell surface in order to cleave extracellular substrates.

scholarly journals Regulation of membrane-type 1 matrix metalloproteinase activity by vacuolar H+-ATPases

2003 ◽  
Vol 373 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Erik MAQUOI ◽  
Karine PEYROLLIER ◽  
Agnès NOËL ◽  
Jean-Michel FOIDART ◽  
Francis FRANKENNE
Keyword(s):  
Cell Surface ◽  
Matrix Metalloproteinase ◽  
Membrane Trafficking ◽  
Degradation Process ◽  
Bafilomycin A1 ◽  
Complex Process ◽  
Autocatalytic Processing ◽  
Key Enzyme ◽  
Membrane Type

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a key enzyme in normal development and malignant processes. The regulation of MT1-MMP activity on the cell surface is a complex process involving autocatalytic processing, tissue inhibitor of MMPs (TIMP) binding and constitutive internalization. However, the fate of internalized MT1-MMP is not known. Acidification of intracellular vacuolar compartments is essential for membrane trafficking, protein sorting and degradation. This acidification is controlled by vacuolar H+-ATPases, which can be selectively inhibited by bafilomycin-A1. Here, we treated human tumour cell lines expressing MT1-MMP with bafilomycin-A1, and analysed its effects on MT1-MMP activity, internalization and processing. We show that the activity of MT1-MMP on the cell surface is constitutively down-regulated through a vacuolar H+-ATPase-dependent degradation process. Blockade of this degradation caused the accumulation of TIMP-free active MT1-MMP molecules on the cell surface, although internalization was not affected. As a consequence of this impaired degradation, pro-MMP-2 activation was strongly enhanced. This study demonstrates that the catalytic activity of MT1-MMP on the cell surface is regulated through a vacuolar H+-ATPase-dependent degradation process.

scholarly journals Rapid Trafficking of Membrane Type 1-Matrix Metalloproteinase to the Cell Surface Regulates Progelatinase A Activation

2002 ◽  
Vol 82 (12) ◽  
pp. 1673-1684 ◽  
Author(s):  
Stanley Zucker ◽  
Michelle Hymowitz ◽  
Cathleen E Conner ◽  
Elizabeth A DiYanni ◽  
Jian Cao
Keyword(s):  
Cell Surface ◽  
Matrix Metalloproteinase ◽  
Membrane Type

scholarly journals Oxidative Stress and Prostate Cancer Progression Are Elicited by Membrane-Type 1 Matrix Metalloproteinase

2011 ◽  
Vol 9 (10) ◽  
pp. 1305-1318 ◽  
Author(s):  
Hoang-Lan Nguyen ◽  
Stanley Zucker ◽  
Kevin Zarrabi ◽  
Pournima Kadam ◽  
Cathleen Schmidt ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prostate Cancer ◽  
Matrix Metalloproteinase ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
Membrane Type

scholarly journals The Oncogenic Response to MiR-335 Is Associated with Cell Surface Expression of Membrane-Type 1 Matrix Metalloproteinase (MT1-MMP) Activity

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0132026 ◽  
Author(s):  
Fausto Rojas ◽  
Maria E. Hernandez ◽  
Milagros Silva ◽  
Lihua Li ◽  
Subbaya Subramanian ◽  
...  
Keyword(s):  
Cell Surface ◽  
Matrix Metalloproteinase ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Membrane Type

scholarly journals Cell surface binding and activation of gelatinase A induced by expression of membrane-type-1-matrix metalloproteinase (MT1-MMP)

FEBS Letters ◽  
1996 ◽  
Vol 385 (3) ◽  
pp. 238-240 ◽  
Author(s):  
Hiroshi Sato ◽  
Takahisa Takino ◽  
Takeshi Kinoshita ◽  
Kazushi Imai ◽  
Yasunori Okada ◽  
...  
Keyword(s):  
Cell Surface ◽  
Matrix Metalloproteinase ◽  
Gelatinase A ◽  
Surface Binding ◽  
Cell Surface Binding ◽  
Membrane Type

scholarly journals Increased Aggressiveness of Human Prostate PC-3 Tumor Cells Expressing Cell Surface Localized Membrane Type-1 Matrix Metalloproteinase (MT1-MMP)

2009 ◽  
Vol 30 (3) ◽  
pp. 259-274 ◽  
Author(s):  
X. Wang ◽  
M. J. Wilson ◽  
J. W. Slaton ◽  
A. A. Sinha ◽  
S. L. Ewing ◽  
...  
Keyword(s):  
Cell Surface ◽  
Matrix Metalloproteinase ◽  
Tumor Cells ◽  
Human Prostate ◽  
Membrane Type

scholarly journals Membrane interactions with membrane type 1 matrix metalloproteinase

2018 ◽  
Author(s):  
◽  
Tara Marcink
Keyword(s):  
Cell Surface ◽  
Matrix Metalloproteinase ◽  
Catalytic Domain ◽  
Membrane Surface ◽  
Membrane Binding ◽  
Tumor Cell Migration ◽  
Peripheral Protein ◽  
Membrane Type ◽  
Dynamics Simulations

Membrane type 1 matrix metalloproteinase (MT1-MMP) is essential to a myriad of extracellular activities including tumor cell migration and angiogenesis. At the cell surface, MT1-MMP is a major factor in the proteolysis of receptors, growth factors, and collagen. MT1-MMP extracellular domains bind the cell surface which can be influential in bringing these complexes together. This study uses new techniques to uncover the interactions between MT1-MMP and the cell surface. Described here is the development of techniques in protein and lipid preparations, NMR data acquisition, and structure determination by molecular dynamics simulations. Through these methods, the HPX domain was shown to bind nanodiscs by opposing tips of blade II and blade IV. The protruding part of these tips contain an EPGYPK sequence that are seen dipping into the membrane surface making contact with the lipid head groups. Blade IV membrane binding allows collagen to bind unhindered. Both blade II and blade IV membrane binding structures are shown to be favorable for homodimerization without disruption of the collagen binding site. The catalytic domain is shown to at least transiently bind membranes. This study then hypothesizes and discusses how these interactions impact both future peripheral protein membrane interaction studies and uncover similarities between the MMP family.

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