The Actin Bundling Protein Fascin-1 as an ACE2-Accessory Protein
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ORIGINAL RESEARCH
The Actin Bundling Protein Fascin‑1 as an ACE2‑Accessory Protein Blessing Ogunlade1 · Jessie J. Guidry2 · Snigdha Mukerjee3 · Srinivas Sriramula4 · Eric Lazartigues3,5,6 · Catalin M. Filipeanu1 Received: 17 June 2020 / Accepted: 20 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords Angiotensin-converting enzyme 2 · Fascin-1 · Actin bundling protein · Internalization · Angiotensin type 1 receptor
Introduction
* Catalin M. Filipeanu [email protected] 1
Department of Pharmacology, College of Medicine, Howard University, 520 W St., NW, Washington, DC 20059, USA
2
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
3
Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
4
Department of Pharmacology and Toxicology, Brody School of Medicine at East Carolina University, 600 Moye Blvd, Greenville, NC 27834, USA
5
Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
6
Southeast Louisiana Veterans Health Care Systems, New Orleans, LA 70119, USA
The renin-angiotensin system (RAS) represents one of the most important therapeutic targets for the treatment of cardiovascular diseases. During the last 20 years, angiotensinconverting enzyme 2 (ACE2) has been shown to contribute to the maintenance of normal cardiovascular function. Its major role includes hydrolysis of angiotensin (Ang)-I and Ang-II to vasodilatory peptides Ang-(1–9) and Ang-(1–7), respectively (Donoghue et al. 2000; Vickers et al. 2002; Xu et al. 2011). Ang-(1–9) and Ang-
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