|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online 11 October 2005
doi: 10.1242/jcs.02610
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Research Article |
The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
* Author for correspondence (e-mail: strongin{at}burnham.org)
Accepted 3 August 2005
Membrane type-1 matrix metalloproteinase (MT1-MMP) degrades the extracellular matrix, initiates the activation pathway of soluble MMPs and regulates the functionality of cell adhesion signaling receptors, thus playing an important role in many cell functions. Intracellular transport mechanisms, currently incompletely understood, regulate the presentation of MT1-MMP at the cell surface. We have focused our efforts on identifying these mechanisms. To understand the transport of MT1-MMP across the cell, we used substitution and deletion mutants, the trafficking of which was examined using antibody uptake and Chariot delivery experiments. Our experiments have demonstrated that the microtubulin cytoskeleton and the centrosomes (the microtubulin cytoskeleton-organizing centers) are essential for the trafficking and the internalization of MT1-MMP. We determined that after reaching the plasma membrane, MT1-MMP is internalized in the Rab-4-positive recycling endosomes and the Rab-11-positive pericentrosomal recycling endosomes. The microtubular trafficking causes the protease to accumulate in the pericentrosomal region of the cell. We believe that the presence of the transmembrane domain is required for the microtubular vesicular trafficking of MT1-MMP because the soluble mutants are not presented at the cell surface and they are not delivered to the centrosomes. The observed transport mechanisms provide a vehicle for the intracellular targets and, accordingly, for an intracellular cleavage function of MT1-MMP in malignant cells, which routinely overexpress this protease.
Key words: MT1-MMP, Chariot delivery, Antibody uptake, Trafficking, Centrosome, Cytoskeleton, Microtubules, Endocytosis, Exocytosis
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  M. J. Kean, K. C. Williams, M. Skalski, D. Myers, A. Burtnik, D. Foster, and M. G. Coppolino VAMP3, syntaxin-13 and SNAP23 are involved in secretion of matrix metalloproteinases, degradation of the extracellular matrix and cell invasion J. Cell Sci., November 15, 2009; 122(22): 4089 - 4098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Poincloux, F. Lizarraga, and P. Chavrier Matrix invasion by tumour cells: a focus on MT1-MMP trafficking to invadopodia J. Cell Sci., September 1, 2009; 122(17): 3015 - 3024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Bass, M. R. Morgan, and M. J. Humphries Syndecans Shed Their Reputation as Inert Molecules Sci. Signal., March 31, 2009; 2(64): pe18 - pe18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ouyang, S. Lu, X.-Y. Li, J. Xu, J. Seong, B. N. G. Giepmans, J. Y.-J. Shyy, S. J. Weiss, and Y. Wang Visualization of Polarized Membrane Type 1 Matrix Metalloproteinase Activity in Live Cells by Fluorescence Resonance Energy Transfer Imaging J. Biol. Chem., June 20, 2008; 283(25): 17740 - 17748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. G. Spinale Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function Physiol Rev, October 1, 2007; 87(4): 1285 - 1342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Spruill, A. S. Lowry, R. E. Stroud, C. E. Squires, I. M. Mains, E. C. Flack, C. Beck, J. S. Ikonomidis, A. J. Crumbley, P. J. McDermott, et al. Membrane-type-1 matrix metalloproteinase transcription and translation in myocardial fibroblasts from patients with normal left ventricular function and from patients with cardiomyopathy Am J Physiol Cell Physiol, October 1, 2007; 293(4): C1362 - C1373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Knoblauch, C. Will, G. Goncharenko, S. Ludwig, and V. Wixler The binding of Mss4 to {alpha}-integrin subunits regulates matrix metalloproteinase activation and fibronectin remodeling FASEB J, February 1, 2007; 21(2): 497 - 510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. S. Golubkov, A. V. Chekanov, A. Y. Savinov, D. V. Rozanov, N. V. Golubkova, and A. Y. Strongin Membrane Type-1 Matrix Metalloproteinase Confers Aneuploidy and Tumorigenicity on Mammary Epithelial Cells Cancer Res., November 1, 2006; 66(21): 10460 - 10465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Remacle, A. V. Chekanov, V. S. Golubkov, A. Y. Savinov, D. V. Rozanov, and A. Y. Strongin O-Glycosylation Regulates Autolysis of Cellular Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) J. Biol. Chem., June 23, 2006; 281(25): 16897 - 16905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Chabottaux, N. E. Sounni, C. J. Pennington, W. R. English, F. van den Brule, S. Blacher, C. Gilles, C. Munaut, E. Maquoi, C. Lopez-Otin, et al. Membrane-type 4 matrix metalloproteinase promotes breast cancer growth and metastases. Cancer Res., May 15, 2006; 66(10): 5165 - 5172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. S. Golubkov, A. V. Chekanov, S. J. Doxsey, and A. Y. Strongin Centrosomal Pericentrin Is a Direct Cleavage Target of Membrane Type-1 Matrix Metalloproteinase in Humans but Not in Mice: POTENTIAL IMPLICATIONS FOR TUMORIGENESIS J. Biol. Chem., December 23, 2005; 280(51): 42237 - 42241. [Abstract] [Full Text] [PDF]
|
|
