ArticleCellular and molecular life sciences : CMLS2013
The substrate degradome of meprin metalloproteases reveals an unexpected proteolytic link between meprin β and ADAM10.
Article in Cellular and molecular life sciences : CMLS, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 125 citations in OpenAlex.
- Ageing impacts extracellular matrix turnover and remodelling in the kidney.Matrix biology plus · 2026Article
- Meprin-β levels are increased in the brain and the cerebrospinal fluid of Alzheimer's disease patients.Alzheimer's research & therapy · 2026Article
- Inflammatory bowel disease and extracellular matrix: when victim becomes double agent.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Meprin proteases in cutaneous homeostasis and psoriasis: pathophysiological mechanisms and therapeutic prospects.Frontiers in immunology · 2026Review
- Meprin β Modulates Brevican Proteolysis Impairing Neural Plasticity and Memory Formation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- HYTANE-Identified Latrophilin-3 Cleavage by Meprin β Leads to Loss of the Interaction Domains.Journal of proteome research · 2025Article
- Targeted approach to determine the impact of cancer-associated protease variants.Science advances · 2025Article
- Alpha-lipoic acid alleviates cognitive deficits in transgenic APP23/PS45 mice through a mitophagy-mediated increase in ADAM10 α-secretase cleavage of APP.Alzheimer's research & therapy · 2024Article
- ThePolymers · 2024Review
- Co-option of an Astacin Metalloprotease Is Associated with an Evolutionarily Novel Feeding Morphology in a Predatory Nematode.Molecular biology and evolution · 2023Article
- The putative pleiotropic functions of meprin β in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2023Article
- Identifying causal serum protein-cardiometabolic trait relationships using whole genome sequencing.Human molecular genetics · 2023Article
- Proteolytic processing of galectin-3 by meprin metalloproteases is crucial for host-microbiome homeostasis.Science advances · 2023Article
- ADAM10-a "multitasker" in sepsis: focus on its posttranslational target.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- The clusterin connectome: Emerging players in chondrocyte biology and putative exploratory biomarkers of osteoarthritis.Frontiers in immunology · 2023Article
- Helical ultrastructure of the metalloprotease meprin α in complex with a small molecule inhibitor.Nature communications · 2022Article
- TAILS Identifies Candidate Substrates and Biomarkers of ADAMTS7, a Therapeutic Protease Target in Coronary Artery Disease.Molecular & cellular proteomics : MCP · 2022Article
- The CCN2/CTGF interactome: an approach to understanding the versatility of CCN2/CTGF molecular activities.Journal of cell communication and signaling · 2021Review
- N-Terminomics Strategies for Protease Substrates Profiling.Molecules (Basel, Switzerland) · 2021Review
- Distinct contributions of meprins to skin regeneration after injury - Meprin α a physiological processer of pro-collagen VII.Matrix biology plus · 2021Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 9 institutions in 4 countries.
Funding
Abstract
The in vivo roles of meprin metalloproteases in pathophysiological conditions remain elusive. Substrates define protease roles. Therefore, to identify natural substrates for human meprin α and β we employed TAILS (terminal amine isotopic labeling of substrates), a proteomics approach that enriches for N-terminal peptides of proteins and cleavage fragments. Of the 151 new extracellular substrates we identified, it was notable that ADAM10 (a disintegrin and metalloprotease domain-containing protein 10)-the constitutive α-secretase-is activated by meprin β through cleavage of the propeptide. To validate this cleavage event, we expressed recombinant proADAM10 and after preincubation with meprin β, this resulted in significantly elevated ADAM10 activity. Cellular expression in murine primary fibroblasts confirmed activation. Other novel substrates including extracellular matrix proteins, growth factors and inhibitors were validated by western analyses and enzyme activity assays with Edman sequencing confirming the exact cleavage sites identified by TAILS. Cleavages in vivo were confirmed by comparing wild-type and meprin(-/-) mice. Our finding of cystatin C, elafin and fetuin-A as substrates and natural inhibitors for meprins reveal new mechanisms in the regulation of protease activity important for understanding pathophysiological processes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.