Usher syndrome proteins ADGRV1 (USH2C) and CIB2 (USH1J) interact and share a common interactome containing TRiC/CCT-BBS chaperonins
The human Usher syndrome (USH) is the most common form of a sensory hereditary ciliopathy characterized by progressive vision and hearing loss. Mutations in the genes ADGRV1 and CIB2 have been associated with two distinct sub-types of USH, namely, USH2C and USH1J. The proteins encoded by the two gen...
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| Format: | Article |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1199069/full |
| _version_ | 1797797817223217152 |
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| author | Joshua Linnert Barbara Knapp Baran E. Güler Karsten Boldt Marius Ueffing Uwe Wolfrum |
| author_facet | Joshua Linnert Barbara Knapp Baran E. Güler Karsten Boldt Marius Ueffing Uwe Wolfrum |
| author_sort | Joshua Linnert |
| collection | DOAJ |
| description | The human Usher syndrome (USH) is the most common form of a sensory hereditary ciliopathy characterized by progressive vision and hearing loss. Mutations in the genes ADGRV1 and CIB2 have been associated with two distinct sub-types of USH, namely, USH2C and USH1J. The proteins encoded by the two genes belong to very distinct protein families: the adhesion G protein-coupled receptor ADGRV1 also known as the very large G protein-coupled receptor 1 (VLGR1) and the Ca2+- and integrin-binding protein 2 (CIB2), respectively. In the absence of tangible knowledge of the molecular function of ADGRV1 and CIB2, pathomechanisms underlying USH2C and USH1J are still unknown. Here, we aimed to enlighten the cellular functions of CIB2 and ADGRV1 by the identification of interacting proteins, a knowledge that is commonly indicative of cellular functions. Applying affinity proteomics by tandem affinity purification in combination with mass spectrometry, we identified novel potential binding partners of the CIB2 protein and compared these with the data set we previously obtained for ADGRV1. Surprisingly, the interactomes of both USH proteins showed a high degree of overlap indicating their integration in common networks, cellular pathways and functional modules which we confirmed by GO term analysis. Validation of protein interactions revealed that ADGRV1 and CIB2 mutually interact. In addition, we showed that the USH proteins also interact with the TRiC/CCT chaperonin complex and the Bardet Biedl syndrome (BBS) chaperonin-like proteins. Immunohistochemistry on retinal sections demonstrated the co-localization of the interacting partners at the photoreceptor cilia, supporting the role of USH proteins ADGRV1 and CIB2 in primary cilia function. The interconnection of protein networks involved in the pathogenesis of both syndromic retinal dystrophies BBS and USH suggest shared pathomechanisms for both syndromes on the molecular level. |
| first_indexed | 2024-03-13T03:55:08Z |
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| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-13T03:55:08Z |
| publishDate | 2023-06-01 |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-b051c4e7f75a4dd8b3aa8b33d9c8634b2023-06-22T07:47:12ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-06-011110.3389/fcell.2023.11990691199069Usher syndrome proteins ADGRV1 (USH2C) and CIB2 (USH1J) interact and share a common interactome containing TRiC/CCT-BBS chaperoninsJoshua Linnert0Barbara Knapp1Baran E. Güler2Karsten Boldt3Marius Ueffing4Uwe Wolfrum5Institute of Molecular Physiology, Molecular Cell Biology, Johannes Gutenberg University Mainz, Mainz, GermanyInstitute of Molecular Physiology, Molecular Cell Biology, Johannes Gutenberg University Mainz, Mainz, GermanyInstitute of Molecular Physiology, Molecular Cell Biology, Johannes Gutenberg University Mainz, Mainz, GermanyInstitute for Ophthalmic Research, Eberhard Karls University of Tuebingen, Tubingen, GermanyInstitute for Ophthalmic Research, Eberhard Karls University of Tuebingen, Tubingen, GermanyInstitute of Molecular Physiology, Molecular Cell Biology, Johannes Gutenberg University Mainz, Mainz, GermanyThe human Usher syndrome (USH) is the most common form of a sensory hereditary ciliopathy characterized by progressive vision and hearing loss. Mutations in the genes ADGRV1 and CIB2 have been associated with two distinct sub-types of USH, namely, USH2C and USH1J. The proteins encoded by the two genes belong to very distinct protein families: the adhesion G protein-coupled receptor ADGRV1 also known as the very large G protein-coupled receptor 1 (VLGR1) and the Ca2+- and integrin-binding protein 2 (CIB2), respectively. In the absence of tangible knowledge of the molecular function of ADGRV1 and CIB2, pathomechanisms underlying USH2C and USH1J are still unknown. Here, we aimed to enlighten the cellular functions of CIB2 and ADGRV1 by the identification of interacting proteins, a knowledge that is commonly indicative of cellular functions. Applying affinity proteomics by tandem affinity purification in combination with mass spectrometry, we identified novel potential binding partners of the CIB2 protein and compared these with the data set we previously obtained for ADGRV1. Surprisingly, the interactomes of both USH proteins showed a high degree of overlap indicating their integration in common networks, cellular pathways and functional modules which we confirmed by GO term analysis. Validation of protein interactions revealed that ADGRV1 and CIB2 mutually interact. In addition, we showed that the USH proteins also interact with the TRiC/CCT chaperonin complex and the Bardet Biedl syndrome (BBS) chaperonin-like proteins. Immunohistochemistry on retinal sections demonstrated the co-localization of the interacting partners at the photoreceptor cilia, supporting the role of USH proteins ADGRV1 and CIB2 in primary cilia function. The interconnection of protein networks involved in the pathogenesis of both syndromic retinal dystrophies BBS and USH suggest shared pathomechanisms for both syndromes on the molecular level.https://www.frontiersin.org/articles/10.3389/fcell.2023.1199069/fullusher syndromebardet biedl syndrome (BBS)protein networksretinal ciliopathiesVLGR1TRiC/CCT chaperonins |
| spellingShingle | Joshua Linnert Barbara Knapp Baran E. Güler Karsten Boldt Marius Ueffing Uwe Wolfrum Usher syndrome proteins ADGRV1 (USH2C) and CIB2 (USH1J) interact and share a common interactome containing TRiC/CCT-BBS chaperonins Frontiers in Cell and Developmental Biology usher syndrome bardet biedl syndrome (BBS) protein networks retinal ciliopathies VLGR1 TRiC/CCT chaperonins |
| title | Usher syndrome proteins ADGRV1 (USH2C) and CIB2 (USH1J) interact and share a common interactome containing TRiC/CCT-BBS chaperonins |
| title_full | Usher syndrome proteins ADGRV1 (USH2C) and CIB2 (USH1J) interact and share a common interactome containing TRiC/CCT-BBS chaperonins |
| title_fullStr | Usher syndrome proteins ADGRV1 (USH2C) and CIB2 (USH1J) interact and share a common interactome containing TRiC/CCT-BBS chaperonins |
| title_full_unstemmed | Usher syndrome proteins ADGRV1 (USH2C) and CIB2 (USH1J) interact and share a common interactome containing TRiC/CCT-BBS chaperonins |
| title_short | Usher syndrome proteins ADGRV1 (USH2C) and CIB2 (USH1J) interact and share a common interactome containing TRiC/CCT-BBS chaperonins |
| title_sort | usher syndrome proteins adgrv1 ush2c and cib2 ush1j interact and share a common interactome containing tric cct bbs chaperonins |
| topic | usher syndrome bardet biedl syndrome (BBS) protein networks retinal ciliopathies VLGR1 TRiC/CCT chaperonins |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1199069/full |
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