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The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell Surface expression

Aiysha Thompson, Venkat Kanamarlapudi Orcid Logo

Scientific Reports, Volume: 4, Start page: 7410

Swansea University Author: Venkat Kanamarlapudi Orcid Logo

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DOI (Published version): 10.1038/srep07410

Abstract

The hGLP-1R is a target for the treatment of type 2 diabetes and belongs to the class B family of GPCRs. Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. This study analysed t...

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Published in: Scientific Reports
Published: 2014
URI: https://cronfa.swan.ac.uk/Record/cronfa19782
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fullrecord <?xml version="1.0"?><rfc1807><datestamp>2019-06-24T13:45:14.6957304</datestamp><bib-version>v2</bib-version><id>19782</id><entry>2014-12-17</entry><title>The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell Surface expression</title><swanseaauthors><author><sid>63741801137148abfa4c00cd547dcdfa</sid><ORCID>0000-0002-8739-1483</ORCID><firstname>Venkat</firstname><surname>Kanamarlapudi</surname><name>Venkat Kanamarlapudi</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2014-12-17</date><deptcode>BMS</deptcode><abstract>The hGLP-1R is a target for the treatment of type 2 diabetes and belongs to the class B family of GPCRs. Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. The N-terminal deletions of hGLP-1R revealed that the HRASP, not the SP, is essential for cell surface expression of GLP-1R. Further, inhibition of hGLP-1R glycosylation prevented cell surface expression of the receptor. Mutation of Trp39, Tyr69 and Tyr88, which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. In conclusion, the N-terminus of hGLP-1R regulates receptor trafficking and maturation. Therefore this study provides insight into the role of hGLP-1R N-terminus on the receptor cell surface expression.</abstract><type>Journal Article</type><journal>Scientific Reports</journal><volume>4</volume><paginationStart>7410</paginationStart><publisher/><keywords/><publishedDay>15</publishedDay><publishedMonth>12</publishedMonth><publishedYear>2014</publishedYear><publishedDate>2014-12-15</publishedDate><doi>10.1038/srep07410</doi><url/><notes></notes><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><apcterm/><lastEdited>2019-06-24T13:45:14.6957304</lastEdited><Created>2014-12-17T15:49:39.2882026</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>Aiysha</firstname><surname>Thompson</surname><order>1</order></author><author><firstname>Venkat</firstname><surname>Kanamarlapudi</surname><orcid>0000-0002-8739-1483</orcid><order>2</order></author></authors><documents/><OutputDurs/></rfc1807>
spelling 2019-06-24T13:45:14.6957304 v2 19782 2014-12-17 The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell Surface expression 63741801137148abfa4c00cd547dcdfa 0000-0002-8739-1483 Venkat Kanamarlapudi Venkat Kanamarlapudi true false 2014-12-17 BMS The hGLP-1R is a target for the treatment of type 2 diabetes and belongs to the class B family of GPCRs. Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. The N-terminal deletions of hGLP-1R revealed that the HRASP, not the SP, is essential for cell surface expression of GLP-1R. Further, inhibition of hGLP-1R glycosylation prevented cell surface expression of the receptor. Mutation of Trp39, Tyr69 and Tyr88, which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. In conclusion, the N-terminus of hGLP-1R regulates receptor trafficking and maturation. Therefore this study provides insight into the role of hGLP-1R N-terminus on the receptor cell surface expression. Journal Article Scientific Reports 4 7410 15 12 2014 2014-12-15 10.1038/srep07410 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2019-06-24T13:45:14.6957304 2014-12-17T15:49:39.2882026 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Aiysha Thompson 1 Venkat Kanamarlapudi 0000-0002-8739-1483 2
title The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell Surface expression
spellingShingle The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell Surface expression
Venkat Kanamarlapudi
title_short The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell Surface expression
title_full The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell Surface expression
title_fullStr The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell Surface expression
title_full_unstemmed The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell Surface expression
title_sort The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell Surface expression
author_id_str_mv 63741801137148abfa4c00cd547dcdfa
author_id_fullname_str_mv 63741801137148abfa4c00cd547dcdfa_***_Venkat Kanamarlapudi
author Venkat Kanamarlapudi
author2 Aiysha Thompson
Venkat Kanamarlapudi
format Journal article
container_title Scientific Reports
container_volume 4
container_start_page 7410
publishDate 2014
institution Swansea University
doi_str_mv 10.1038/srep07410
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 0
active_str 0
description The hGLP-1R is a target for the treatment of type 2 diabetes and belongs to the class B family of GPCRs. Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. The N-terminal deletions of hGLP-1R revealed that the HRASP, not the SP, is essential for cell surface expression of GLP-1R. Further, inhibition of hGLP-1R glycosylation prevented cell surface expression of the receptor. Mutation of Trp39, Tyr69 and Tyr88, which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. In conclusion, the N-terminus of hGLP-1R regulates receptor trafficking and maturation. Therefore this study provides insight into the role of hGLP-1R N-terminus on the receptor cell surface expression.
published_date 2014-12-15T03:23:18Z
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score 11.017797

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