Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1
Abstract Scribble (Scrib) is a multidomain polarity protein and member of the leucine-rich repeat and PDZ domain (LAP) protein family. A loss of Scrib expression is associated with disturbed apical-basal polarity and tumor formation. The tumor-suppressive activity of Scrib correlates with its membra...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Portfolio
2023-07-01
|
Series: | Communications Biology |
Online Access: | https://doi.org/10.1038/s42003-023-05088-3 |
_version_ | 1797778684084486144 |
---|---|
author | Eva-Maria Thüring Christian Hartmann Janesha C. Maddumage Airah Javorsky Birgitta E. Michels Volker Gerke Lawrence Banks Patrick O. Humbert Marc Kvansakul Klaus Ebnet |
author_facet | Eva-Maria Thüring Christian Hartmann Janesha C. Maddumage Airah Javorsky Birgitta E. Michels Volker Gerke Lawrence Banks Patrick O. Humbert Marc Kvansakul Klaus Ebnet |
author_sort | Eva-Maria Thüring |
collection | DOAJ |
description | Abstract Scribble (Scrib) is a multidomain polarity protein and member of the leucine-rich repeat and PDZ domain (LAP) protein family. A loss of Scrib expression is associated with disturbed apical-basal polarity and tumor formation. The tumor-suppressive activity of Scrib correlates with its membrane localization. Despite the identification of numerous Scrib-interacting proteins, the mechanisms regulating its membrane recruitment are not fully understood. Here, we identify the cell adhesion receptor TMIGD1 as a membrane anchor of Scrib. TMIGD1 directly interacts with Scrib through a PDZ domain-mediated interaction and recruits Scrib to the lateral membrane domain in epithelial cells. We characterize the association of TMIGD1 with each Scrib PDZ domain and describe the crystal structure of the TMIGD1 C-terminal peptide complexed with PDZ domain 1 of Scrib. Our findings describe a mechanism of Scrib membrane localization and contribute to the understanding of the tumor-suppressive activity of Scrib. |
first_indexed | 2024-03-12T23:20:59Z |
format | Article |
id | doaj.art-1f98da77c25844a090ea916faeec5541 |
institution | Directory Open Access Journal |
issn | 2399-3642 |
language | English |
last_indexed | 2024-03-12T23:20:59Z |
publishDate | 2023-07-01 |
publisher | Nature Portfolio |
record_format | Article |
series | Communications Biology |
spelling | doaj.art-1f98da77c25844a090ea916faeec55412023-07-16T11:25:12ZengNature PortfolioCommunications Biology2399-36422023-07-016111510.1038/s42003-023-05088-3Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1Eva-Maria Thüring0Christian Hartmann1Janesha C. Maddumage2Airah Javorsky3Birgitta E. Michels4Volker Gerke5Lawrence Banks6Patrick O. Humbert7Marc Kvansakul8Klaus Ebnet9Institute-associated Research Group “Cell adhesion and cell polarity”, Institute of Medical Biochemistry, ZMBE, University of MünsterInstitute-associated Research Group “Cell adhesion and cell polarity”, Institute of Medical Biochemistry, ZMBE, University of MünsterDepartment of Biochemistry & Chemistry, La Trobe Institute for Molecular Science, La Trobe UniversityDepartment of Biochemistry & Chemistry, La Trobe Institute for Molecular Science, La Trobe UniversityInstitute-associated Research Group “Cell adhesion and cell polarity”, Institute of Medical Biochemistry, ZMBE, University of MünsterInstitute of Medical Biochemistry, ZMBE, University of MünsterInternational Centre for Genetic Engineering and BiotechnologyDepartment of Biochemistry & Chemistry, La Trobe Institute for Molecular Science, La Trobe UniversityDepartment of Biochemistry & Chemistry, La Trobe Institute for Molecular Science, La Trobe UniversityInstitute-associated Research Group “Cell adhesion and cell polarity”, Institute of Medical Biochemistry, ZMBE, University of MünsterAbstract Scribble (Scrib) is a multidomain polarity protein and member of the leucine-rich repeat and PDZ domain (LAP) protein family. A loss of Scrib expression is associated with disturbed apical-basal polarity and tumor formation. The tumor-suppressive activity of Scrib correlates with its membrane localization. Despite the identification of numerous Scrib-interacting proteins, the mechanisms regulating its membrane recruitment are not fully understood. Here, we identify the cell adhesion receptor TMIGD1 as a membrane anchor of Scrib. TMIGD1 directly interacts with Scrib through a PDZ domain-mediated interaction and recruits Scrib to the lateral membrane domain in epithelial cells. We characterize the association of TMIGD1 with each Scrib PDZ domain and describe the crystal structure of the TMIGD1 C-terminal peptide complexed with PDZ domain 1 of Scrib. Our findings describe a mechanism of Scrib membrane localization and contribute to the understanding of the tumor-suppressive activity of Scrib.https://doi.org/10.1038/s42003-023-05088-3 |
spellingShingle | Eva-Maria Thüring Christian Hartmann Janesha C. Maddumage Airah Javorsky Birgitta E. Michels Volker Gerke Lawrence Banks Patrick O. Humbert Marc Kvansakul Klaus Ebnet Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1 Communications Biology |
title | Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1 |
title_full | Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1 |
title_fullStr | Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1 |
title_full_unstemmed | Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1 |
title_short | Membrane recruitment of the polarity protein Scribble by the cell adhesion receptor TMIGD1 |
title_sort | membrane recruitment of the polarity protein scribble by the cell adhesion receptor tmigd1 |
url | https://doi.org/10.1038/s42003-023-05088-3 |
work_keys_str_mv | AT evamariathuring membranerecruitmentofthepolarityproteinscribblebythecelladhesionreceptortmigd1 AT christianhartmann membranerecruitmentofthepolarityproteinscribblebythecelladhesionreceptortmigd1 AT janeshacmaddumage membranerecruitmentofthepolarityproteinscribblebythecelladhesionreceptortmigd1 AT airahjavorsky membranerecruitmentofthepolarityproteinscribblebythecelladhesionreceptortmigd1 AT birgittaemichels membranerecruitmentofthepolarityproteinscribblebythecelladhesionreceptortmigd1 AT volkergerke membranerecruitmentofthepolarityproteinscribblebythecelladhesionreceptortmigd1 AT lawrencebanks membranerecruitmentofthepolarityproteinscribblebythecelladhesionreceptortmigd1 AT patrickohumbert membranerecruitmentofthepolarityproteinscribblebythecelladhesionreceptortmigd1 AT marckvansakul membranerecruitmentofthepolarityproteinscribblebythecelladhesionreceptortmigd1 AT klausebnet membranerecruitmentofthepolarityproteinscribblebythecelladhesionreceptortmigd1 |