Academic Journal
Low Density Lipoprotein Receptor Variants in the Beta-Propeller Subdomain and Their Functional Impact
| العنوان: | Low Density Lipoprotein Receptor Variants in the Beta-Propeller Subdomain and Their Functional Impact |
|---|---|
| المؤلفون: | Lucie Dušková, Lucie Nohelová, Tomáš Loja, Jana Fialová, Petra Zapletalová, Kamila Réblová, Lukáš Tichý, Tomáš Freiberger, Lenka Fajkusová |
| المصدر: | Frontiers in Genetics, Vol 11 (2020) |
| بيانات النشر: | Frontiers Media S.A. |
| سنة النشر: | 2020 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | low density lipoprotein receptor, live cell imaging microscopy, flow cytometry, functional analysis, ER stress, Genetics, QH426-470 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1664-8021 |
| Relation: | https://www.frontiersin.org/article/10.3389/fgene.2020.00691/full; https://doaj.org/toc/1664-8021; https://doaj.org/article/e0b1b4537abe45e4844fcda7349ffdb8 |
| DOI: | 10.3389/fgene.2020.00691 |
| الاتاحة: | https://doi.org/10.3389/fgene.2020.00691 https://doaj.org/article/e0b1b4537abe45e4844fcda7349ffdb8 |
| رقم الانضمام: | edsbas.E2FF08B0 |
| قاعدة البيانات: | BASE |
Full Text Finder | ResultId |
1 |
|---|---|
| Header |
edsbas BASE edsbas.E2FF08B0 905 3 Academic Journal academicJournal 905.017944335938 |
| PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsbas&AN=edsbas.E2FF08B0&custid=s6537998&authtype=sso |
| FullText |
Array
(
[Availability] => 0
)
Array ( [0] => Array ( [Url] => https://doi.org/10.3389/fgene.2020.00691# [Name] => EDS - BASE [Category] => fullText [Text] => View record in BASE [MouseOverText] => View record in BASE ) [1] => Array ( [Url] => https://resolver.ebscohost.com/openurl?custid=s6537998&groupid=main&authtype=ip,guest&sid=EBSCO:edsbas&genre=article&issn=16648021&ISBN=&volume=&issue=&date=20200101&spage=&pages=&title=Frontiers in Genetics, Vol 11 (2020&atitle=Low%20Density%20Lipoprotein%20Receptor%20Variants%20in%20the%20Beta-Propeller%20Subdomain%20and%20Their%20Functional%20Impact&id=DOI:10.3389/fgene.2020.00691 [Name] => Full Text Finder (s6537998api) [Category] => fullText [Text] => Full Text Finder [Icon] => https://imageserver.ebscohost.com/branding/images/FTF.gif [MouseOverText] => Full Text Finder ) ) |
| Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => Low Density Lipoprotein Receptor Variants in the Beta-Propeller Subdomain and Their Functional Impact
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Lucie+Dušková%22">Lucie Dušková</searchLink><br /><searchLink fieldCode="AR" term="%22Lucie+Nohelová%22">Lucie Nohelová</searchLink><br /><searchLink fieldCode="AR" term="%22Tomáš+Loja%22">Tomáš Loja</searchLink><br /><searchLink fieldCode="AR" term="%22Jana+Fialová%22">Jana Fialová</searchLink><br /><searchLink fieldCode="AR" term="%22Petra+Zapletalová%22">Petra Zapletalová</searchLink><br /><searchLink fieldCode="AR" term="%22Kamila+Réblová%22">Kamila Réblová</searchLink><br /><searchLink fieldCode="AR" term="%22Lukáš+Tichý%22">Lukáš Tichý</searchLink><br /><searchLink fieldCode="AR" term="%22Tomáš+Freiberger%22">Tomáš Freiberger</searchLink><br /><searchLink fieldCode="AR" term="%22Lenka+Fajkusová%22">Lenka Fajkusová</searchLink> ) Array ( [Name] => TitleSource [Label] => Source [Group] => Src [Data] => Frontiers in Genetics, Vol 11 (2020) ) Array ( [Name] => Publisher [Label] => Publisher Information [Group] => PubInfo [Data] => Frontiers Media S.A. ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2020 ) Array ( [Name] => Subset [Label] => Collection [Group] => HoldingsInfo [Data] => Directory of Open Access Journals: DOAJ Articles ) Array ( [Name] => Subject [Label] => Subject Terms [Group] => Su [Data] => <searchLink fieldCode="DE" term="%22low+density+lipoprotein+receptor%22">low density lipoprotein receptor</searchLink><br /><searchLink fieldCode="DE" term="%22live+cell+imaging+microscopy%22">live cell imaging microscopy</searchLink><br /><searchLink fieldCode="DE" term="%22flow+cytometry%22">flow cytometry</searchLink><br /><searchLink fieldCode="DE" term="%22functional+analysis%22">functional analysis</searchLink><br /><searchLink fieldCode="DE" term="%22ER+stress%22">ER stress</searchLink><br /><searchLink fieldCode="DE" term="%22Genetics%22">Genetics</searchLink><br /><searchLink fieldCode="DE" term="%22QH426-470%22">QH426-470</searchLink> ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => 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. ) Array ( [Name] => TypeDocument [Label] => Document Type [Group] => TypDoc [Data] => article in journal/newspaper ) Array ( [Name] => Language [Label] => Language [Group] => Lang [Data] => English ) Array ( [Name] => ISSN [Label] => ISSN [Group] => ISSN [Data] => 1664-8021 ) Array ( [Name] => NoteTitleSource [Label] => Relation [Group] => SrcInfo [Data] => https://www.frontiersin.org/article/10.3389/fgene.2020.00691/full; https://doaj.org/toc/1664-8021; https://doaj.org/article/e0b1b4537abe45e4844fcda7349ffdb8 ) Array ( [Name] => DOI [Label] => DOI [Group] => ID [Data] => 10.3389/fgene.2020.00691 ) Array ( [Name] => URL [Label] => Availability [Group] => URL [Data] => https://doi.org/10.3389/fgene.2020.00691<br />https://doaj.org/article/e0b1b4537abe45e4844fcda7349ffdb8 ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsbas.E2FF08B0 ) |
| RecordInfo |
Array
(
[BibEntity] => Array
(
[Identifiers] => Array
(
[0] => Array
(
[Type] => doi
[Value] => 10.3389/fgene.2020.00691
)
)
[Languages] => Array
(
[0] => Array
(
[Text] => English
)
)
[Subjects] => Array
(
[0] => Array
(
[SubjectFull] => low density lipoprotein receptor
[Type] => general
)
[1] => Array
(
[SubjectFull] => live cell imaging microscopy
[Type] => general
)
[2] => Array
(
[SubjectFull] => flow cytometry
[Type] => general
)
[3] => Array
(
[SubjectFull] => functional analysis
[Type] => general
)
[4] => Array
(
[SubjectFull] => ER stress
[Type] => general
)
[5] => Array
(
[SubjectFull] => Genetics
[Type] => general
)
[6] => Array
(
[SubjectFull] => QH426-470
[Type] => general
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Low Density Lipoprotein Receptor Variants in the Beta-Propeller Subdomain and Their Functional Impact
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Lucie Dušková
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Lucie Nohelová
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Tomáš Loja
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Jana Fialová
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Petra Zapletalová
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Kamila Réblová
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Lukáš Tichý
)
)
)
[7] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Tomáš Freiberger
)
)
)
[8] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Lenka Fajkusová
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 01
[M] => 01
[Type] => published
[Y] => 2020
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-print
[Value] => 16648021
)
[1] => Array
(
[Type] => issn-locals
[Value] => edsbas
)
[2] => Array
(
[Type] => issn-locals
[Value] => edsbas.oa
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Frontiers in Genetics, Vol 11 (2020
[Type] => main
)
)
)
)
)
)
)
|
| IllustrationInfo |