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| http://dx.doi.org/10.4161/chan.29659 | DOI Listing |
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Calcium-sensing receptor- and ADAM10-mediated klotho shedding is regulated by tetraspanin 5.
FEBS Lett
January 2025
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Soluble, circulating Klotho (sKlotho) is essential for normal health and renal function. sKlotho is shed from the renal distal convoluted tubule (DCT), its primary source, via enzymatic cleavage. However, the physiologic mechanisms that control sKlotho production, trafficking, and shedding are not fully defined.
View Article and Find Full Text PDFSite-specific analysis and functional characterization of N-linked glycosylation for β-Klotho protein.
Int J Biol Macromol
December 2024
State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, 21 Sassoon Road, Pokfulam 999077, Hong Kong, China; Department of Medicine, School of Clinical Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam 999077, Hong Kong, China; Department of Pharmacology and Pharmacy, The University of Hong Kong, 21 Sassoon Road, Pokfulam 999077, Hong Kong, China. Electronic address:
β-Klotho (KLB), a type I transmembrane protein, serves as an obligate co-receptor determining the tissue-specific actions of endocrine fibroblast growth factors (FGFs). Despite accumulative evidence suggesting the occurrence of N-glycosylation in the KLB protein, the precise N-glycosites, glycoforms, and the impacts of N-glycosylation on the expression and function of the KLB protein remain unexplored. Employing a mass spectrometry-based approach, a total of 12 N-glycosites displaying heterogeneous site occupancy and glycoforms were identified within the extracellular region of the recombinant human KLB protein.
View Article and Find Full Text PDFAsparagine614 Determines the Transport and Function of the Murine Anti-Aging Protein Klotho.
Cells
October 2024
Leibniz Institut für Alternsforschung-Fritz Lipmann Institut, 07745 Jena, Germany.
Klotho is an anti-aging protein whose deletion significantly reduces lifespan in mice, while its over-expression increases lifespan. Klotho is a type-I transmembrane protein that is N-glycosylated at eight positions within its ectodomain. Our study demonstrates that N-glycosylation or mutation at position N614, but not at N161, N285, or N346 in mouse Klotho, is critically involved in the transport of Klotho out of the endoplasmic reticulum (ER).
View Article and Find Full Text PDFProtective genes and pathways in Alzheimer's disease: moving towards precision interventions.
Mol Neurodegener
April 2021
Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, 1207 17th Ave S, Nashville, TN, 37212, USA.
Alzheimer's disease (AD) is a progressive, neurodegenerative disorder that is characterized by neurodegeneration, cognitive impairment, and an eventual inability to perform daily tasks. The etiology of Alzheimer's is complex, with numerous environmental and genetic factors contributing to the disease. Late-onset AD is highly heritable (60 to 80%), and over 40 risk loci for AD have been identified via large genome-wide association studies, most of which are common variants with small effect sizes.
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