Related Experiment Video
Updated: Jun 2, 2026
07:09
Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
MT1-MMP cleaves Dll1 to negatively regulate Notch signalling to maintain normal B-cell development
Guoxiang Jin1, Fengju Zhang, Kui Ming Chan
1Department of Biochemistry, Center for Reproduction, Development and Growth, The University of Hong Kong, Pok Fu Lam, Hong Kong.
The EMBO Journal
|May 17, 2011
Summary
Loss of MT1-MMP in bone marrow stromal cells enhances Notch signaling, impairing B-lymphocyte development. MT1-MMP cleaves Dll1, regulating Notch and maintaining normal B-cell production.
Area of Science:
- Hematology
- Cell Biology
- Molecular Biology
Background:
- Notch signaling is crucial for hematopoietic progenitor cell (HPC) differentiation.
- Bone marrow stromal cells (BMSCs) play a key role in regulating hematopoiesis.
Purpose of the Study:
- To investigate the role of membrane-type 1 matrix metalloproteinase (MT1-MMP) in B-lymphocyte development.
- To elucidate the mechanism by which MT1-MMP influences Notch signaling in HPCs.
Main Methods:
- Co-culture of HPCs with wild-type and MT1-MMP-deficient BMSCs.
- In vitro and in vivo studies using Notch signaling inhibitor DAPT.
- Analysis of MT1-MMP interaction with Notch ligand Delta-like 1 (Dll1).
Main Results:
- MT1-MMP deficiency in BMSCs increased Notch signaling in HPCs, impairing B-lymphocyte differentiation.
- DAPT treatment rescued B-lymphocyte development defects both in vitro and in vivo.
- MT1-MMP directly cleaves Dll1 on the cell surface, reducing Notch signaling.
Conclusions:
- MT1-MMP acts as a negative regulator of Notch signaling by cleaving Dll1.
- This MT1-MMP-mediated regulation is essential for normal B-cell development in the bone marrow.
Related Concept Videos
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
01:23Role 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...
A...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...