Teneurin C-Terminal Associated Peptide (TCAP)-1 and Latrophilin Interaction in HEK293 Cells: Evidence for Modulation of Intercellular Adhesion
The teneurins are a family of four transmembrane proteins essential to intercellular adhesion processes, and are required for the development and maintenance of tissues. The Adhesion G protein-coupled receptor (GPCR) subclass latrophilins (ADGRL), or simply the latrophilins (LPHN), are putative rece...
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| Format: | Article |
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2019.00022/full |
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| author | Mia Husić Dalia Barsyte-Lovejoy David A. Lovejoy |
| author_facet | Mia Husić Dalia Barsyte-Lovejoy David A. Lovejoy |
| author_sort | Mia Husić |
| collection | DOAJ |
| description | The teneurins are a family of four transmembrane proteins essential to intercellular adhesion processes, and are required for the development and maintenance of tissues. The Adhesion G protein-coupled receptor (GPCR) subclass latrophilins (ADGRL), or simply the latrophilins (LPHN), are putative receptors of the teneurins and act, in part, to mediate intercellular adhesion via binding with the teneurin extracellular region. At the distal tip of the extracellular region of each teneurin lies a peptide sequence termed the teneurin C-terminal associated peptide (TCAP). TCAP-1, associated with teneurin-1, is itself bioactive, suggesting that TCAP is a critical functional region of teneurin. However, the role of TCAP-1 has not been established with respect to its ability to interact with LPHN to induce downstream effects. To establish that TCAP-1 binds to LPHN1, a FLAG-tagged hormone binding domain (HBD) of LPHN1 and a GFP-tagged TCAP-1 peptide were co-expressed in HEK293 cells. Both immunoreactive epitopes were co-localized as a single band after immunoprecipitation, indicating an association between the two proteins. Moreover, fluorescent co-labeling occurred at the plasma membrane of LPHN1 over-expressing cells when treated with a FITC-tagged TCAP-1 variant. Expression of LPHN1 and treatment with TCAP-1 modulated the actin-based cytoskeleton in these cells in a manner consistent with previously reported actions of TCAP-1 and affected the overall morphology and aggregation of the cells. This study indicates that TCAP-1 may associate directly with LPHN1 and could play a role in the modulation of cytoskeletal organization and intercellular adhesion and aggregation via this interaction. |
| first_indexed | 2024-12-21T17:35:19Z |
| format | Article |
| id | doaj.art-959045a6e805411a9e2df9deb493e133 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-21T17:35:19Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-959045a6e805411a9e2df9deb493e1332022-12-21T18:55:47ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922019-02-011010.3389/fendo.2019.00022419196Teneurin C-Terminal Associated Peptide (TCAP)-1 and Latrophilin Interaction in HEK293 Cells: Evidence for Modulation of Intercellular AdhesionMia Husić0Dalia Barsyte-Lovejoy1David A. Lovejoy2Department of Cell and Systems Biology, University of Toronto, Toronto, ON, CanadaStructural Genomics Consortium, University of Toronto, Toronto, ON, CanadaDepartment of Cell and Systems Biology, University of Toronto, Toronto, ON, CanadaThe teneurins are a family of four transmembrane proteins essential to intercellular adhesion processes, and are required for the development and maintenance of tissues. The Adhesion G protein-coupled receptor (GPCR) subclass latrophilins (ADGRL), or simply the latrophilins (LPHN), are putative receptors of the teneurins and act, in part, to mediate intercellular adhesion via binding with the teneurin extracellular region. At the distal tip of the extracellular region of each teneurin lies a peptide sequence termed the teneurin C-terminal associated peptide (TCAP). TCAP-1, associated with teneurin-1, is itself bioactive, suggesting that TCAP is a critical functional region of teneurin. However, the role of TCAP-1 has not been established with respect to its ability to interact with LPHN to induce downstream effects. To establish that TCAP-1 binds to LPHN1, a FLAG-tagged hormone binding domain (HBD) of LPHN1 and a GFP-tagged TCAP-1 peptide were co-expressed in HEK293 cells. Both immunoreactive epitopes were co-localized as a single band after immunoprecipitation, indicating an association between the two proteins. Moreover, fluorescent co-labeling occurred at the plasma membrane of LPHN1 over-expressing cells when treated with a FITC-tagged TCAP-1 variant. Expression of LPHN1 and treatment with TCAP-1 modulated the actin-based cytoskeleton in these cells in a manner consistent with previously reported actions of TCAP-1 and affected the overall morphology and aggregation of the cells. This study indicates that TCAP-1 may associate directly with LPHN1 and could play a role in the modulation of cytoskeletal organization and intercellular adhesion and aggregation via this interaction.https://www.frontiersin.org/article/10.3389/fendo.2019.00022/fullTCAPteneurinlatrophilinLPHNGPCRreceptor-ligand interaction |
| spellingShingle | Mia Husić Dalia Barsyte-Lovejoy David A. Lovejoy Teneurin C-Terminal Associated Peptide (TCAP)-1 and Latrophilin Interaction in HEK293 Cells: Evidence for Modulation of Intercellular Adhesion Frontiers in Endocrinology TCAP teneurin latrophilin LPHN GPCR receptor-ligand interaction |
| title | Teneurin C-Terminal Associated Peptide (TCAP)-1 and Latrophilin Interaction in HEK293 Cells: Evidence for Modulation of Intercellular Adhesion |
| title_full | Teneurin C-Terminal Associated Peptide (TCAP)-1 and Latrophilin Interaction in HEK293 Cells: Evidence for Modulation of Intercellular Adhesion |
| title_fullStr | Teneurin C-Terminal Associated Peptide (TCAP)-1 and Latrophilin Interaction in HEK293 Cells: Evidence for Modulation of Intercellular Adhesion |
| title_full_unstemmed | Teneurin C-Terminal Associated Peptide (TCAP)-1 and Latrophilin Interaction in HEK293 Cells: Evidence for Modulation of Intercellular Adhesion |
| title_short | Teneurin C-Terminal Associated Peptide (TCAP)-1 and Latrophilin Interaction in HEK293 Cells: Evidence for Modulation of Intercellular Adhesion |
| title_sort | teneurin c terminal associated peptide tcap 1 and latrophilin interaction in hek293 cells evidence for modulation of intercellular adhesion |
| topic | TCAP teneurin latrophilin LPHN GPCR receptor-ligand interaction |
| url | https://www.frontiersin.org/article/10.3389/fendo.2019.00022/full |
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