β-Adrenergic receptors (βARs) are the principal mediators of catecholamine action in cardiomyocytes. We previously showed that βARs accumulate as both full-length and NH-terminally truncated species in cells, that maturational processing of full-length βARs to an NH-terminally truncated form is attributable to -glycan-regulated proteolytic cleavage of the βAR NH-terminus at R ↓ L by ADAM17, and that NH-terminally truncated βARs remain signaling competent but they acquire a distinct signaling phenotype. NH-terminally truncated βARs differ from full-length βARs in their signaling bias to cAMP/PKA versus ERK pathways and only the NH-terminally truncated form of the βAR constitutively activates AKT and confers protection against doxorubicin-dependent apoptosis in cardiomyocytes. Since the R ↓ L sequence conforms to a trypsin consensus cleavage site, we used immunoblotting methods to test the hypothesis that βARs are also cleaved at R ↓ L by trypsin (an enzyme typically used to isolate cardiomyocytes from the intact ventricle). We show that full-length βARs are cleaved by trypsin and that trypsin cleaves the full-length βAR NH-terminus specifically at R ↓ L in CHO-Pro5 cells. Trypsin also cleaves βARs in cardiomyocytes, but at a second site that results in the formation of ∼40-kDa NH-terminal and ∼30-kDa COOH-terminal fragments. The observation that cardiomyocyte βARs are cleaved by trypsin (a mechanism that constitutes a heretofore-unrecognized mechanism that would influence βAR-signaling responses) suggests that studies that use standard trypsin-based procedures to isolate adult cardiomyocytes from the intact ventricle should be interpreted with caution. Current concepts regarding the molecular basis for βAR responses derive from literature predicated on the assumption that βARs signal exclusively as full-length receptor proteins. However, we recently showed that βARs accumulate as both full-length and NH-terminally truncated forms. This manuscript provides novel evidence that β-adrenergic receptors can be cleaved by trypsin and that cell surface βAR cleavage constitutes a heretofore unrecognized mechanism to alter catecholamine-dependent signaling responses.
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http://dx.doi.org/10.1152/ajpheart.00005.2022 | DOI Listing |
Magn Reson Med
January 2025
Department of Radiology, University of Missouri, Columbia, Missouri, USA.
Purpose: The aim of the work is to develop a cascaded diffusion-based super-resolution model for low-resolution (LR) MR tagging acquisitions, which is integrated with parallel imaging to achieve highly accelerated MR tagging while enhancing the tag grid quality of low-resolution images.
Methods: We introduced TagGen, a diffusion-based conditional generative model that uses low-resolution MR tagging images as guidance to generate corresponding high-resolution tagging images. The model was developed on 50 patients with long-axis-view, high-resolution tagging acquisitions.
Nat Commun
January 2025
State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Helmholtz International Lab for Anti-infectives, Shandong University-Helmholtz Institute of Biotechnology, Shandong University, Qingdao, Shandong, China.
Modular polyketide synthases (mPKSs) are multidomain enzymes in bacteria that synthesize a variety of pharmaceutically important compounds. mPKS genes are usually longer than 10 kb and organized in operons. To understand the transcriptional and translational characteristics of these large genes, here we split the 13-kb busA gene, encoding a 456-kDa three-module PKS for butenyl-spinosyn biosynthesis, into three smaller separately translated genes encoding one PKS module in an operon.
View Article and Find Full Text PDFJ Med Genet
January 2025
Department of Pediatrics, NHO Beppu Medical Center, Beppu, Oita, Japan
Introduction: Genotype-phenotype correlations in -related neurodevelopmental disorders (-NDDs) remain unclear. This systematic review aimed to clarify these correlations.
Methods: Searches of PubMed and Embase were conducted on 8 August 2024 to identify studies that had investigated genetically diagnosed NDDs (5q31.
Int J Biol Macromol
January 2025
College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, PR China. Electronic address:
As a Group 2B carcinogen, accurate and efficient detection for Fumonisin B1 (FB1) is essential. The emergence of aptamers presents a viable solution to meet this demand. In this study, a truncated aptamer named Apt40 was developed, showcasing remarkable binding affinity to FB1.
View Article and Find Full Text PDFAm J Hum Genet
January 2025
Genetics Institute, Rambam Health Care Campus, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Electronic address:
Pathogenic heterozygous variants in CHD4 cause Sifrim-Hitz-Weiss syndrome, a neurodevelopmental disorder associated with brain anomalies, heart defects, macrocephaly, hypogonadism, and additional features with variable expressivity. Most individuals have non-recurrent missense variants, complicating variant interpretation. A few were reported with truncating variants, and their role in disease is unclear.
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