Low Density Lipoprotein Receptor Variants in the Beta-Propeller Subdomain and Their Functional Impact
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209775%3A_____%2F20%3AN0000001" target="_blank" >RIV/00209775:_____/20:N0000001 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14110/20:00116330 RIV/65269705:_____/20:00072867
Result on the web
<a href="https://www.frontiersin.org/articles/10.3389/fgene.2020.00691/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fgene.2020.00691/full</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3389/fgene.2020.00691" target="_blank" >10.3389/fgene.2020.00691</a>
Alternative languages
Result language
angličtina
Original language name
Low Density Lipoprotein Receptor Variants in the Beta-Propeller Subdomain and Their Functional Impact
Original language description
Pathogenic variants in the low density lipoprotein receptor gene are associated with familial hypercholesterolemia. Some of these variants can result in incorrect folding of the LDLR protein, which is then accumulated inside the cell and cannot fulfill its function to internalize LDL particles. We analyzed the functional impact of 10 LDLR variants localized in the beta-propeller of epidermal growth factor precursor homology domain. The experimental part of the work was complemented by a structural analysis on the basis of 3D LDLR protein structure.T-Rex Chinese hamster ovary cells transfected with the human LDLR gene were used for live cell imaging microscopy, flow cytometry, and qRT-PCR analysis. Our results showed that the analyzed LDLR protein variants can be divided into three groups. (1) The variants buried inside the 3D protein structure expressing proteins accumulated in the endoplasmic reticulum (ER) with no or reduced plasma membrane localization and LDL particle internalization, and associated with an increased gene expression of ER-resident chaperones. (2) The variants localized on the surface of 3D protein structure with slightly reduced LDLR plasma membrane localization and LDL particle internalization, and associated with no increased mRNA level of ER-resident chaperones. (3) The variants localized on the surface of the 3D protein structure but expressing proteins with cell responses similar to the group 1. All analyzed LDLR variants have been evaluated as pathogenic but with different effects on protein localization and function, and expression of genes associated with ER stress.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30101 - Human genetics
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Frontiers in Genetics
ISSN
1664-8021
e-ISSN
—
Volume of the periodical
11
Issue of the periodical within the volume
June 2020
Country of publishing house
CH - SWITZERLAND
Number of pages
10
Pages from-to
Article 691
UT code for WoS article
000618730600001
EID of the result in the Scopus database
2-s2.0-85087885705