ArticleInvestigative ophthalmology & visual science2010
Functional role of proteolytic processing of recombinant myocilin in self-aggregation.
Article in Investigative ophthalmology & visual science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Transgenic Overexpression of Myocilin Leads to Variable Ocular Anterior Segment and Retinal Alterations Associated with Extracellular Matrix Abnormalities in Adult Zebrafish.International journal of molecular sciences · 2022Article
- Molecular architecture and modifications of full-length myocilin.Experimental eye research · 2021Article
- The Potential Role of Small-Molecule PERK Inhibitor LDN-0060609 in Primary Open-Angle Glaucoma Treatment.International journal of molecular sciences · 2021Article
- Knockout ofBiology · 2021Article
- The Genetic and Endoplasmic Reticulum-Mediated Molecular Mechanisms of Primary Open-Angle Glaucoma.International journal of molecular sciences · 2020Review
- Physiological function of myocilin and its role in the pathogenesis of glaucoma in the trabecular meshwork (Review).International journal of molecular medicine · 2019Review
- Identification of myocilin as a blood plasma protein and analysis of its role in leukocyte adhesion to endothelial cell monolayers.PloS one · 2018Article
- Common and rare genetic risk factors for glaucoma.Cold Spring Harbor perspectives in medicine · 2014Review
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- Keeping an eye on myocilin: a complex molecule associated with primary open-angle glaucoma susceptibility.Molecules (Basel, Switzerland) · 2011Review
- Interaction of recombinant myocilin with the matricellular protein SPARC: functional implications.Investigative ophthalmology & visual science · 2011Article
- Glaucoma: genes, phenotypes, and new directions for therapy.The Journal of clinical investigation · 2010Review
- The effects of myocilin expression on functionally relevant trabecular meshwork genes: a mini-review.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and TherapeuticsReview
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeRecombinant myocilin expressed in cells in culture is endoproteolytically cleaved in the endoplasmic reticulum by calpain II, releasing an N-terminal and a C-terminal fragment. This proteolytic processing has been speculated to regulate the molecular interactions of myocilin. The main purpose of this study was to analyze the effect of the proteolytic cleavage on myocilin aggregation.
methodscDNAs encoding human myocilin and the N- and C-terminal fragments were transiently expressed in HEK-293T cells. Covalent interactions of recombinant myocilin were analyzed by SDS-PAGE and Western immunoblot analysis in different dissociating conditions. Noncovalent interactions were studied by solid-phase binding assays, performed with Ni-chelating HPLC-purified recombinant proteins, and by Far-Western blot analysis.
resultsWestern blot analysis of recombinant myocilin aggregates under either increasing ionic strength or increasing concentration of reducing agent indicated that ionic interactions do not contribute to the stability of the molecular complexes linked by disulfide bridges. Disulfide myocilin homoaggregates decreased as the proteolytic processing increased. Solid-phase binding assays showed the existence of high-affinity (K(d) = 0.068 microM) noncovalent myocilin-myocilin interactions and that processed fragments bound to the full-length protein with significantly reduced affinity. Far-Western blot analysis confirmed noncovalent interactions between recombinant myocilin disulfide aggregates.
conclusionsThe proteolytic processing of recombinant myocilin decreases myocilin homoaggregates. These data provide the first evidence of a functional role for this processing in myocilin aggregation and suggest that disulfide complexes of myocilin could organize into a dynamic extracellular network sustained by noncovalent N-terminal interactions.
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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.