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Related Concept Videos

Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
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Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Energy to Drive Translocation01:37

Energy to Drive Translocation

Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Overview of Cell-Matrix Interactions01:24

Overview of Cell-Matrix Interactions

The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
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Cell-matrix's Response to Mechanical Forces

In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
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Related Experiment Video

Updated: Jul 13, 2026

Reconstitution of Msp1 Extraction Activity with Fully Purified Components
05:52

Reconstitution of Msp1 Extraction Activity with Fully Purified Components

Published on: August 10, 2021

Activation-coupled membrane-type 1 matrix metalloproteinase membrane trafficking.

Yi I Wu1, Hidayatullah G Munshi, Scott J Snipas

  • 1Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

The Biochemical Journal
|July 26, 2007
PubMed
Summary

A novel alpha1-proteinase inhibitor (alpha1-PI(MT1)) effectively blocks membrane-type 1 matrix metalloproteinase (MT1-MMP) activation by inhibiting furin. This leads to reduced MT1-MMP activity, collagen invasion, and altered intracellular localization of proMT1-MMP.

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Last Updated: Jul 13, 2026

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05:52

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Published on: August 10, 2021

2D and 3D Matrices to Study Linear Invadosome Formation and Activity
12:25

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Published on: June 2, 2017

Using Cell-substrate Impedance and Live Cell Imaging to Measure Real-time Changes in Cellular Adhesion and De-adhesion Induced by Matrix Modification
09:11

Using Cell-substrate Impedance and Live Cell Imaging to Measure Real-time Changes in Cellular Adhesion and De-adhesion Induced by Matrix Modification

Published on: February 19, 2015

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP-14) is crucial for development and cancer progression.
  • MT1-MMP activity is tightly regulated at the post-translational level, particularly during zymogen activation.
  • Inhibiting MT1-MMP activation is a potential therapeutic strategy for cancers.

Purpose of the Study:

  • To design and evaluate a novel alpha1-proteinase inhibitor (alpha1-PI(MT1)) targeting MT1-MMP activation.
  • To investigate the effects of alpha1-PI(MT1) on proMT1-MMP activation, MT1-MMP activity, and cell-surface localization.
  • To compare the efficacy of alpha1-PI(MT1) with wild-type alpha1-PI (alpha1-PI(WT)) and a furin inhibitory mutant alpha1-PI(PDX).

Main Methods:

  • Engineered alpha1-PI(MT1) by incorporating the MT1-MMP propeptide cleavage sequence into the alpha1-PI reactive-site loop.
  • Assessed the interaction of alpha1-PI(MT1) with furin and its effect on proMT1-MMP activation using SDS-stable complex formation.
  • Evaluated MT1-MMP-mediated collagen invasion and the subcellular localization of proMT1-MMP in cells expressing alpha1-PI(MT1).

Main Results:

  • Alpha1-PI(MT1) formed an SDS-stable complex with furin, effectively inhibiting proMT1-MMP activation.
  • MT1-MMP activity was reduced, leading to decreased MT1-MMP-mediated collagen invasion and proMMP-2 activation.
  • Expression of alpha1-PI(MT1) caused intracellular accumulation of a glycosylated proMT1-MMP species, retaining it in the perinuclear region and reducing cell-surface presence.

Conclusions:

  • Alpha1-PI(MT1) is a potent inhibitor of MT1-MMP zymogen activation by targeting furin.
  • MT1-MMP activity and subcellular localization are coordinately regulated, with intracellular retention of proMT1-MMP prior to activation.
  • Targeting MT1-MMP activation and localization presents a promising strategy for controlling cancer progression and invasion.