Smith JL, Reloj AR, Nataraj PS, Bartos DC, Schroder EA, Moss AJ, Ohno S, Horie M, Anderson CL, January CT, Delisle BP. Pharmacological correction of long QT-linked mutations in KCNH2 (hERG) increases the trafficking of Kv11.1 channels stored in the transitional endoplasmic reticulum.
The human ether-a-go-go related gene (hERG) encodes the voltage-gated K(+) channel that underlies the rapidly activating delayed-rectifier current in cardiac myocytes. hERG is synthesized in the endoplasmic reticulum (ER) as an "immature" N-linked glycoprotein and is terminally glycosylated in the Golgi apparatus. Most hERG missense mutations linked to long QT syndrome type 2 (LQT2) reduce the terminal glycosylation and functional expression. We tested the hypothesis that a distinct pre-Golgi compartment negatively regulates the trafficking of some LQT2 mutations to the Golgi apparatus. We found that treating cells in nocodazole, a microtubule depolymerizing agent, altered the subcellular localization, functional expression, and glycosylation of the LQT2 mutation G601S-hERG differently from wild-type hERG (WT-hERG). G601S-hERG quickly redistributed to peripheral compartments that partially colocalized with KDEL (Lys-Asp-Glu-Leu) chaperones but not calnexin, Sec31, or the ER golgi intermediate compartment (ERGIC). Treating cells in E-4031, a drug that increases the functional expression of G601S-hERG, prevented the accumulation of G601S-hERG to the peripheral compartments and increased G601S-hERG colocalization with the ERGIC. Coexpressing the temperature-sensitive mutant G protein from vesicular stomatitis virus, a mutant N-linked glycoprotein that is retained in the ER, showed it was not restricted to the same peripheral compartments as G601S-hERG at nonpermissive temperatures. We conclude that the trafficking of G601S-hERG is negatively regulated by a microtubule-dependent compartment within the ER. Identifying mechanisms that prevent the sorting or promote the release of LQT2 channels from this compartment may represent a novel therapeutic strategy for LQT2.
Fruits and vegetables are nutritious and good in minerals, vitamins, and fib. Most fresh fruits and vegetables contain a minimum of 70% of moisture content which causes the formation of bacteria, fungi, and viruses to affect and cause the items to rot. But dried fruits contain only less than 20% of moisture content. So drying the fruits and vegetables helps to preserve the items for longer use without causing them to rot. Dried fruits have a great source of antioxidants and help in health benefits like improving blood flow, and reducing the effects of many diseases. Compared to fresh fruits, dried fruits are good in nutrition and have less weight for packaging and transportation usage. For drying materials, various types of solar dryers are used. Natural or open sun drying methods comparatively consume more than 12 h to dry material, whereas, direct and indirect drying methods would enhance the efficiency and dry the products quicker than open drying. For the consideration of quality drying and to increase efficiency, various modifications of solar dryers are designed and fabricated. In this review, we discussed the most appropriate developments in the drying of food items, required phase change materials (PCMs), performance, and environmental analysis of SD, and also reported the various designs of the solar drying techniques.
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