scholarly journals Site-directed MT1-MMP trafficking and surface insertion regulate AChR clustering and remodeling at developing NMJs

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Zora Chui-Kuen Chan ◽  
Hiu-Lam Rachel Kwan ◽  
Yin Shun Wong ◽  
Zhixin Jiang ◽  
Zhongjun Zhou ◽  
...  
Keyword(s):  
Neuromuscular Junctions ◽  
Physiological Role ◽  
Structural Defects ◽  
Ecm Proteins ◽  
Ecm Degradation ◽  
Membrane Type ◽  
Postsynaptic Differentiation ◽  
Achr Clustering

At vertebrate neuromuscular junctions (NMJs), the synaptic basal lamina contains different extracellular matrix (ECM) proteins and synaptogenic factors that induce and maintain synaptic specializations. Here, we report that podosome-like structures (PLSs) induced by ubiquitous ECM proteins regulate the formation and remodeling of acetylcholine receptor (AChR) clusters via focal ECM degradation. Mechanistically, ECM degradation is mediated by PLS-directed trafficking and surface insertion of membrane-type 1 matrix metalloproteinase (MT1-MMP) to AChR clusters through microtubule-capturing mechanisms. Upon synaptic induction, MT1-MMP plays a crucial role in the recruitment of aneural AChR clusters for the assembly of postsynaptic specializations. Lastly, the structural defects of NMJs in embryonic MT1-MMP-/- mice further demonstrate the physiological role of MT1-MMP in normal NMJ development. Collectively, this study suggests that postsynaptic MT1-MMP serves as a molecular switch to synaptogenesis by modulating local ECM environment for the deposition of synaptogenic signals that regulate postsynaptic differentiation at developing NMJs.

scholarly journals SNAP23, Syntaxin4, and vesicle-associated membrane protein 7 (VAMP7) mediate trafficking of membrane type 1–matrix metalloproteinase (MT1-MMP) during invadopodium formation and tumor cell invasion

2014 ◽  
Vol 25 (13) ◽  
pp. 2061-2070 ◽  
Author(s):  
Karla C. Williams ◽  
Rachael E. McNeilly ◽  
Marc G. Coppolino
Keyword(s):  
Membrane Protein ◽  
Matrix Metalloproteinase ◽  
Cell Invasion ◽  
Cellular Invasion ◽  
Protein Receptor ◽  
Ecm Degradation ◽  
Membrane Type ◽  
Regulated Trafficking

Movement through the extracellular matrix (ECM) requires cells to degrade ECM components, primarily through the action of matrix metalloproteinases (MMPs). Membrane type 1–matrix metalloproteinase (MT1-MMP) has an essential role in matrix degradation and cell invasion and localizes to subcellular degradative structures termed invadopodia. Trafficking of MT1-MMP to invadopodia is required for the function of these structures, and here we examine the role of N-ethylmaleimide–sensitive factor–activating protein receptor (SNARE)–mediated membrane traffic in the transport of MT1-MMP to invadopodia. During invadopodium formation in MDA-MB-231 human breast cancer cells, increased association of SNAP23, Syntaxin4, and vesicle-associated membrane protein 7 (VAMP7) is detected by coimmunoprecipitation. Blocking the function of these SNAREs perturbs invadopodium-based ECM degradation and cell invasion. Increased level of SNAP23-Syntaxin4-VAMP7 interaction correlates with decreased Syntaxin4 phosphorylation. These results reveal an important role for SNARE-regulated trafficking of MT1-MMP to invadopodia during cellular invasion of ECM.

scholarly journals Piezo1 mediates angiogenesis through activation of MT1-MMP signaling

2019 ◽  
Vol 316 (1) ◽  
pp. C92-C103 ◽  
Author(s):  
Hojin Kang ◽  
Zhigang Hong ◽  
Ming Zhong ◽  
Jennifer Klomp ◽  
Kayla J. Bayless ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Matrix Metalloproteinase ◽  
Matrix Metalloproteinase 2 ◽  
Sprouting Angiogenesis ◽  
Sphingosine 1 Phosphate ◽  
Wall Shear ◽  
Membrane Type

Angiogenesis is initiated in response to a variety of external cues, including mechanical and biochemical stimuli; however, the underlying signaling mechanisms remain unclear. Here, we investigated the proangiogenic role of the endothelial mechanosensor Piezo1. Genetic deletion and pharmacological inhibition of Piezo1 reduced endothelial sprouting and lumen formation induced by wall shear stress and proangiogenic mediator sphingosine 1-phosphate, whereas Piezo1 activation by selective Piezo1 activator Yoda1 enhanced sprouting angiogenesis. Similarly to wall shear stress, sphingosine 1-phosphate functioned by activating the Ca2+ gating function of Piezo1, which in turn signaled the activation of the matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase during sprouting angiogenesis. Studies in mice in which Piezo1 was conditionally deleted in endothelial cells demonstrated the requisite role of sphingosine 1-phosphate-dependent activation of Piezo1 in mediating angiogenesis in vivo. These results taken together suggest that both mechanical and biochemical stimuli trigger Piezo1-mediated Ca2+ influx and thereby activate matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase and synergistically facilitate sprouting angiogenesis.

scholarly journals Evidence for a cooperative role of gelatinase A and membrane type-1 matrix metalloproteinase during Xenopus laevis development

2007 ◽  
Vol 124 (1) ◽  
pp. 11-22 ◽  
Author(s):  
Takashi Hasebe ◽  
Rebecca Hartman ◽  
Liezhen Fu ◽  
Tosikazu Amano ◽  
Yun-Bo Shi
Keyword(s):  
Xenopus Laevis ◽  
Matrix Metalloproteinase ◽  
Gelatinase A ◽  
Membrane Type

scholarly journals Proinsulin C-peptide - A Consensus Statement

2001 ◽  
Vol 2 (2) ◽  
pp. 145-151 ◽  
Author(s):  
Anders A. F. Sima ◽  
George Grunberger ◽  
Hans Jörnvall ◽  
John Wahren ◽  
The C-Peptide Study Group
Keyword(s):  
Physiological Role ◽  
Biological Action ◽  
Clinical Effects ◽  
State University ◽  
C Peptide ◽  
Wayne State University ◽  
Therapeutic Value ◽  
Diabetes Center

In recent years the physiological role of the proinsulin C-peptide has received increasing attention, focusing on the potential therapeutic value of C-peptide replacement in preventing and ameliorating type 1 diabetic complications. In order to consolidate these new data and to identify the immediate directions of C-peptide research and its clinical usefulness, an International Symposium was held in Detroit, Michigan, on October 20–21, 2000, under the auspices of the Wayne State University/Morris Hood Jr. Comprehensive Diabetes Center. In this communication, we review the cellular, physiological and clinical effects of C-peptide replacement in animal models and in patients with type 1 diabetes. Finally, recommendations are presented as to the most urgent studies that should be pursued to further establish the biological action of C-peptide and its therapeutic value.

scholarly journals Conversion of Stationary to Invasive Tumor Initiating Cells (TICs): Role of Hypoxia in Membrane Type 1-Matrix Metalloproteinase (MT1-MMP) Trafficking

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e38403 ◽  
Author(s):  
Jian Li ◽  
Stanley Zucker ◽  
Ashleigh Pulkoski-Gross ◽  
Cem Kuscu ◽  
Mihriban Karaayvaz ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Tumor Initiating Cells ◽  
Invasive Tumor ◽  
Membrane Type

scholarly journals Selective function-blocking monoclonal human antibody highlights the important role of membrane type-1 matrix metalloproteinase (MT1-MMP) in metastasis

Oncotarget ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 2781-2799 ◽  
Author(s):  
Albert G. Remacle ◽  
Piotr Cieplak ◽  
Dong Hyun Nam ◽  
Sergey A. Shiryaev ◽  
Xin Ge ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Human Antibody ◽  
Membrane Type

scholarly journals The Expanding Role of MT1-MMP in Cancer Progression

2019 ◽  
Vol 12 (2) ◽  
pp. 77 ◽  
Author(s):  
Anna M. Knapinska ◽  
Gregg B. Fields
Keyword(s):  
Transcription Factor ◽  
Immune Responses ◽  
Cancer Progression ◽  
Negative Regulator ◽  
Fibrillar Collagen ◽  
Biological Functions ◽  
Complete Mapping ◽  
Membrane Type

For over 20 years, membrane type 1 matrix metalloproteinase (MT1-MMP) has been recognized as a key component in cancer progression. Initially, the primary roles assigned to MT1-MMP were the activation of proMMP-2 and degradation of fibrillar collagen. Proteomics has revealed a great array of MT1-MMP substrates, and MT1-MMP selective inhibitors have allowed for a more complete mapping of MT1-MMP biological functions. MT1-MMP has extensive sheddase activities, is both a positive and negative regulator of angiogenesis, can act intracellularly and as a transcription factor, and modulates immune responses. We presently examine the multi-faceted role of MT1-MMP in cancer, with a consideration of how the diversity of MT1-MMP behaviors impacts the application of MT1-MMP inhibitors.

Sign in / Sign up

Export Citation Format

Share Document