ArticleThe Journal of biological chemistry2009
Formation of Pmel17 amyloid is regulated by juxtamembrane metalloproteinase cleavage, and the resulting C-terminal fragment is a substrate for gamma-secretase.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 60 citations in OpenAlex.
- Bidirectional regulation of glycoprotein nonmetastatic melanoma protein B by β-glucocerebrosidase deficiency inbioRxiv : the preprint server for biology · 2025Article
- Disrupting the Repeat Domain of Premelanosome Protein (PMEL) Produces Dysamyloidosis and Dystrophic Ocular Pigment Reflective of Pigmentary Glaucoma.International journal of molecular sciences · 2023Article
- sPmel17 Secreted by Ultraviolet B-Exposed Melanocytes Alters the Intercellular Adhesion of Keratinocytes.Oxidative medicine and cellular longevity · 2022Article
- Functional Domains and Evolutionary History of the PMEL and GPNMB Family Proteins.Molecules (Basel, Switzerland) · 2021Article
- Contribution of ADAM17 and related ADAMs in cardiovascular diseases.Cellular and molecular life sciences : CMLS · 2021Review
- Multifunctional Amyloids in the Biology of Gram-Positive Bacteria.Microorganisms · 2020Review
- Functional Amyloids Are the Rule Rather Than the Exception in Cellular Biology.Microorganisms · 2020Review
- Functional Mammalian Amyloids and Amyloid-Like Proteins.Life (Basel, Switzerland) · 2020Review
- Why Study Functional Amyloids? Lessons from the Repeat Domain of Pmel17.Journal of molecular biology · 2018Review
- The zebrafish orthologue of familial Alzheimer's disease gene PRESENILIN 2 is required for normal adult melanotic skin pigmentation.PloS one · 2018Article
- Why are Functional Amyloids Non-Toxic in Humans?Biomolecules · 2017Review
- SheddomeDB: the ectodomain shedding database for membrane-bound shed markers.BMC bioinformatics · 2017Review
- Melanosomal formation of PMEL core amyloid is driven by aromatic residues.Scientific reports · 2017Article
- Regulation of Alpha-Secretase ADAM10Frontiers in molecular neuroscience · 2017Review
- PMEL Amyloid Fibril Formation: The Bright Steps of Pigmentation.International journal of molecular sciences · 2016Review
- Study of Exosomes Shed New Light on Physiology of Amyloidogenesis.Cellular and molecular neurobiology · 2016Review
- The Kringle-like Domain Facilitates Post-endoplasmic Reticulum Changes to Premelanosome Protein (PMEL) Oligomerization and Disulfide Bond Configuration and Promotes Amyloid Formation.The Journal of biological chemistry · 2016Article
- Emerging roles of extracellular vesicles in the nervous system.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Review
- Fold modulating function: bacterial toxins to functional amyloids.Frontiers in microbiology · 2014Review
- The PKD domain distinguishes the trafficking and amyloidogenic properties of the pigment cell protein PMEL and its homologue GPNMB.Pigment cell & melanoma research · 2013Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The formation of insoluble cross beta-sheet amyloid is pathologically associated with disorders such as Alzheimer, Parkinson, and Huntington diseases. One exception is the nonpathological amyloid derived from the protein Pmel17 within melanosomes to generate melanin pigment. Here we show that the formation of insoluble MalphaC intracellular fragments of Pmel17, which are the direct precursors to Pmel17 amyloid, depends on a novel juxtamembrane cleavage at amino acid position 583 between the furin-like proprotein convertase cleavage site and the transmembrane domain. The resulting Pmel17 C-terminal fragment is then processed by the gamma-secretase complex to release a short-lived intracellular domain fragment. Thus, by analogy to the Notch receptor, we designate this cleavage the S2 cleavage site, whereas gamma-secretase mediates proteolysis at the intramembrane S3 site. Substitutions or deletions at this S2 cleavage site, the use of the metalloproteinase inhibitor TAPI-2, as well as small interfering RNA-mediated knock-down of the metalloproteinases ADAM10 and 17 reduced the formation of insoluble Pmel17 fragments. These results demonstrate that the release of the Pmel17 ectodomain, which is critical for melanin amyloidogenesis, is initiated by S2 cleavage at a juxtamembrane position.
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Registered trials
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.