The Actin Bundling Protein Fascin-1 as an ACE2-Accessory Protein.

Autor: Ogunlade B; Department of Pharmacology, College of Medicine, Howard University, 520 W St., NW, Washington, DC, 20059, USA., Guidry JJ; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA., Mukerjee S; Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA., Sriramula S; Department of Pharmacology and Toxicology, Brody School of Medicine at East Carolina University, 600 Moye Blvd, Greenville, NC, 27834, USA., Lazartigues E; Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA.; Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA.; Southeast Louisiana Veterans Health Care Systems, New Orleans, LA, 70119, USA., Filipeanu CM; Department of Pharmacology, College of Medicine, Howard University, 520 W St., NW, Washington, DC, 20059, USA. Catalin.Filipeanu@Howard.edu.
Jazyk: angličtina
Zdroj: Cellular and molecular neurobiology [Cell Mol Neurobiol] 2022 Jan; Vol. 42 (1), pp. 255-263. Date of Electronic Publication: 2020 Aug 31.
DOI: 10.1007/s10571-020-00951-x
Abstrakt: We have previously shown that angiotensin-converting enzyme 2 (ACE2), an enzyme counterbalancing the deleterious effects of angiotensin type 1 receptor activation by production of vasodilatory peptides Angiotensin (Ang)-(1-9) and Ang-(1-7), is internalized and degraded in lysosomes following chronic Ang-II treatment. However, the molecular mechanisms involved in this effect remain unknown. In an attempt to identify the accessory proteins involved in this effect, we conducted a proteomic analysis in ACE2-transfected HEK293T cells. A single protein, fascin-1, was found to differentially interact with ACE2 after Ang-II treatment for 4 h. The interactions between fascin-1 and ACE2 were confirmed by confocal microscopy and co-immunoprecipitation. Overexpression of fascin-1 attenuates the effects of Ang-II on ACE2 activity. In contrast, downregulation of fascin-1 severely decreased ACE2 enzymatic activity. Interestingly, in brain homogenates from hypertensive mice, we observed a significant reduction of fascin-1, suggesting that the levels of this protein may change in cardiovascular diseases. In conclusion, we identified fascin-1 as an ACE2-accessory protein, interacting with the enzyme in an Ang-II dependent manner and contributing to the regulation of enzyme activity.
(© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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