Detailed Information on Publication Record
2020
Low Density Lipoprotein Receptor Variants in the Beta-Propeller Subdomain and Their Functional Impact
DUŠKOVÁ, Lucie, Lucie NOHELOVÁ, Tomáš LOJA, Jana FIALOVÁ, Petra ZAPLETALOVÁ et. al.Basic information
Original name
Low Density Lipoprotein Receptor Variants in the Beta-Propeller Subdomain and Their Functional Impact
Authors
DUŠKOVÁ, Lucie (203 Czech Republic), Lucie NOHELOVÁ (203 Czech Republic), Tomáš LOJA (703 Slovakia, belonging to the institution), Jana FIALOVÁ (203 Czech Republic, belonging to the institution), Petra ZAPLETALOVÁ (203 Czech Republic), Kamila RÉBLOVÁ (203 Czech Republic, belonging to the institution), Lukáš TICHÝ (203 Czech Republic), Tomáš FREIBERGER (203 Czech Republic, guarantor, belonging to the institution) and Lenka FAJKUSOVÁ (203 Czech Republic, belonging to the institution)
Edition
Frontiers in Genetics, Laussane, FRONTIERS MEDIA SA, 2020, 1664-8021
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
10603 Genetics and heredity
Country of publisher
Switzerland
Confidentiality degree
není předmětem státního či obchodního tajemství
References:
Impact factor
Impact factor: 4.599
RIV identification code
RIV/00216224:14110/20:00116330
Organization unit
Faculty of Medicine
UT WoS
000618730600001
Keywords in English
low density lipoprotein receptor; live cell imaging microscopy; flow cytometry; functional analysis; ER stress
Tags
International impact, Reviewed
Změněno: 9/10/2024 12:47, Mgr. Adéla Pešková
Abstract
V originále
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.
Links
| LQ1601, research and development project |
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| 90062, large research infrastructures |
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