Related Experiment Video

Updated: Aug 29, 2026

Generating a Fractal Microstructure of Laminin-111 to Signal to Cells
06:56

Generating a Fractal Microstructure of Laminin-111 to Signal to Cells

Published on: September 28, 2020

Proteolytic processing of laminin-5 by MT1-MMP in tissues and its effects on epithelial cell morphology

Naohiko Koshikawa1, Susann Schenk, Gilbert Moeckel

  • 1The Scripps Research Institute, Department of Cell Biology, La Jolla California, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|December 23, 2003
PubMed

Insights

Matrix metalloproteinase MT1-MMP cleaves laminin-5 in vivo, impacting epithelial organization and differentiation. This study reveals MT1-MMP

Area of Science:

  • Biochemistry
  • Cell Biology
  • Developmental Biology

Background:

  • Laminin-5 (Ln-5) is an extracellular matrix protein crucial for epithelial adhesion and migration.
  • Matrix metalloproteinases (MMPs), including MT1-MMP, are known to process extracellular matrix components in vitro.
  • The in vivo role of MT1-MMP in Ln-5 processing and its impact on epithelial biology remained unclear.

Purpose of the Study:

  • To investigate the in vivo cleavage of laminin-5 by MT1-MMP.
  • To determine the functional consequences of MT1-MMP-mediated Ln-5 processing on epithelial organization and morphology.
  • To establish Ln-5 as a physiological substrate for MT1-MMP.

Main Methods:

  • Analysis of MT1-MMP knockout (KO) mice kidneys for Ln-5 subunit levels and epithelial differentiation.
  • Reconstitution of MT1-MMP expression in a Ln-5 positive, MT1-MMP deficient epithelial cell line via transfection.
  • In vitro cleavage assays using recombinant MT1-MMP and Ln-5 gamma2 constructs.

Main Results:

  • MT1-MMP KO mice exhibited increased total Ln-5 gamma2 subunit but reduced gamma2' form, with poorly differentiated kidney tubular epithelia.
  • MT1-MMP transfectants showed increased processed Ln-5 gamma2 chain and enhanced cell spreading on Ln-5.
  • Recombinant MT1-MMP cleaved Ln-5 gamma2 at a known in vivo processing site.

Conclusions:

  • Laminin-5 is a physiological substrate of MT1-MMP in vivo.
  • MT1-MMP-mediated proteolytic processing of Ln-5 influences epithelial basement membrane turnover.
  • This processing is critical for proper epithelial morphogenesis and tissue organization.

More Related Videos

Preparation of 3D Decellularized Matrices from Fetal Mouse Skeletal Muscle for Cell Culture07:44

Preparation of 3D Decellularized Matrices from Fetal Mouse Skeletal Muscle for Cell Culture

Published on: March 3, 2023

Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence06:23

Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence

Published on: January 17, 2025

Related Concept Videos

Laminins are the Adhesive Proteins of Basal Lamina00:55

Laminins are the Adhesive Proteins of Basal Lamina

Laminins are heterotrimeric proteins with high molecular mass found in the extracellular matrix. Each laminin molecule is composed of three chains, viz. alpha, beta, and gamma, coded by five, four, and three paralogous genes, respectively. Laminins are categories based on the compositions of the three chains.
In humans, the five forms of alpha chains are LAMA 1, LAMA 2, LAMA 3, LAMA 4, and LAMA 5. The four forms of beta chains are LAMB 1, LAMB 2, LAMB 3, and LAMB 4. The three forms of gamma...
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
Mechanism of Lamellipodia Formation01:31

Mechanism of Lamellipodia Formation

Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
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...
The Extracellular Matrix01:29

The Extracellular Matrix

Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
The Extracellular Matrix01:42

The Extracellular Matrix

In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.Composition of the Extracellular MatrixThe extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse molecules.