| DUŠKOVÁ, Lucie, Lucie NOHELOVÁ, Tomáš LOJA, Jana FIALOVÁ, Petra ZAPLETALOVÁ, Kamila RÉBLOVÁ, Lukáš TICHÝ, Tomáš FREIBERGER and Lenka FAJKUSOVÁ. Low Density Lipoprotein Receptor Variants in the Beta-Propeller Subdomain and Their Functional Impact. Frontiers in Genetics. Laussane: FRONTIERS MEDIA SA, 2020, vol. 11, JUN 2020, p. 1-10. ISSN 1664-8021. Available from: https://dx.doi.org/10.3389/fgene.2020.00691. |
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@article{1677117,
author = {Dušková, Lucie and Nohelová, Lucie and Loja, Tomáš and Fialová, Jana and Zapletalová, Petra and Réblová, Kamila and Tichý, Lukáš and Freiberger, Tomáš and Fajkusová, Lenka},
article_location = {Laussane},
article_number = {JUN 2020},
doi = {http://dx.doi.org/10.3389/fgene.2020.00691},
keywords = {low density lipoprotein receptor; live cell imaging microscopy; flow cytometry; functional analysis; ER stress},
language = {eng},
issn = {1664-8021},
journal = {Frontiers in Genetics},
title = {Low Density Lipoprotein Receptor Variants in the Beta-Propeller Subdomain and Their Functional Impact},
url = {https://www.frontiersin.org/articles/10.3389/fgene.2020.00691/full},
volume = {11},
year = {2020}
}
TY - JOUR
ID - 1677117
AU - Dušková, Lucie - Nohelová, Lucie - Loja, Tomáš - Fialová, Jana - Zapletalová, Petra - Réblová, Kamila - Tichý, Lukáš - Freiberger, Tomáš - Fajkusová, Lenka
PY - 2020
TI - Low Density Lipoprotein Receptor Variants in the Beta-Propeller Subdomain and Their Functional Impact
JF - Frontiers in Genetics
VL - 11
IS - JUN 2020
SP - 1-10
EP - 1-10
PB - FRONTIERS MEDIA SA
SN - 16648021
KW - low density lipoprotein receptor
KW - live cell imaging microscopy
KW - flow cytometry
KW - functional analysis
KW - ER stress
UR - https://www.frontiersin.org/articles/10.3389/fgene.2020.00691/full
L2 - https://www.frontiersin.org/articles/10.3389/fgene.2020.00691/full
N2 - Background: 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. Methods: 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. Results: 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. Conclusion: 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.
ER -
DUŠKOVÁ, Lucie, Lucie NOHELOVÁ, Tomáš LOJA, Jana FIALOVÁ, Petra ZAPLETALOVÁ, Kamila RÉBLOVÁ, Lukáš TICHÝ, Tomáš FREIBERGER and Lenka FAJKUSOVÁ. Low Density Lipoprotein Receptor Variants in the Beta-Propeller Subdomain and Their Functional Impact. \textit{Frontiers in Genetics}. Laussane: FRONTIERS MEDIA SA, 2020, vol.~11, JUN 2020, p.~1-10. ISSN~1664-8021. Available from: https://dx.doi.org/10.3389/fgene.2020.00691.
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