Transducin Partners Outside the Phototransduction Pathway
Transducin mediates signal transduction in a classical G protein-coupled receptor (GPCR) phototransduction cascade. Interactions of transducin with the receptor and the effector molecules had been extensively investigated and are currently defined at the atomic level. However, partners and functions...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2020.589494/full |
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| author | Dhiraj Srivastava Ravi P. Yadav Shivangi M. Inamdar Zhen Huang Maxim Sokolov Kimberly Boyd Nikolai O. Artemyev Nikolai O. Artemyev |
| author_facet | Dhiraj Srivastava Ravi P. Yadav Shivangi M. Inamdar Zhen Huang Maxim Sokolov Kimberly Boyd Nikolai O. Artemyev Nikolai O. Artemyev |
| author_sort | Dhiraj Srivastava |
| collection | DOAJ |
| description | Transducin mediates signal transduction in a classical G protein-coupled receptor (GPCR) phototransduction cascade. Interactions of transducin with the receptor and the effector molecules had been extensively investigated and are currently defined at the atomic level. However, partners and functions of rod transducin α (Gαt1) and βγ (Gβ1γ1) outside the visual pathway are not well-understood. In particular, light-induced redistribution of rod transducin from the outer segment to the inner segment and synaptic terminal (IS/ST) allows Gαt1 and/or Gβ1γ1 to modulate synaptic transmission from rods to rod bipolar cells (RBCs). Protein-protein interactions underlying this modulation are largely unknown. We discuss known interactors of transducin in the rod IS/ST compartment and potential pathways leading to the synaptic effects of light-dispersed Gαt1 and Gβ1γ1. Furthermore, we show that a prominent non-GPCR guanine nucleotide exchange factor (GEF) and a chaperone of Gα subunits, resistance to inhibitors of cholinesterase 8A (Ric-8A) protein, is expressed throughout the retina including photoreceptor cells. Recent structures of Ric-8A alone and in complexes with Gα subunits have illuminated the structural underpinnings of the Ric-8A activities. We generated a mouse model with conditional knockout of Ric-8A in rods in order to begin defining the functional roles of the protein in rod photoreceptors and the retina. Our analysis suggests that Ric-8A is not an obligate chaperone of Gαt1. Further research is needed to investigate probable roles of Ric-8A as a GEF, trafficking chaperone, or a mediator of the synaptic effects of Gαt1. |
| first_indexed | 2024-12-10T13:53:14Z |
| format | Article |
| id | doaj.art-87277b3e108444508fb5a654a73265f5 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-10T13:53:14Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-87277b3e108444508fb5a654a73265f52022-12-22T01:46:06ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022020-10-011410.3389/fncel.2020.589494589494Transducin Partners Outside the Phototransduction PathwayDhiraj Srivastava0Ravi P. Yadav1Shivangi M. Inamdar2Zhen Huang3Maxim Sokolov4Kimberly Boyd5Nikolai O. Artemyev6Nikolai O. Artemyev7Department of Molecular Physiology and Biophysics, The University of Iowa Carver College of Medicine, Iowa City, IA, United StatesDepartment of Molecular Physiology and Biophysics, The University of Iowa Carver College of Medicine, Iowa City, IA, United StatesDepartment of Molecular Physiology and Biophysics, The University of Iowa Carver College of Medicine, Iowa City, IA, United StatesDepartment of Neurology and Neuroscience, University of Wisconsin-Madison, Madison, WI, United StatesDepartment of Ophthalmology, Biochemistry and Neuroscience, West Virginia University, Morgantown, WV, United StatesDepartment of Molecular Physiology and Biophysics, The University of Iowa Carver College of Medicine, Iowa City, IA, United StatesDepartment of Molecular Physiology and Biophysics, The University of Iowa Carver College of Medicine, Iowa City, IA, United StatesDepartment of Ophthalmology and Visual Sciences, Ophthalmology and Visual Sciences, The University of Iowa Carver College of Medicine, Iowa City, IA, United StatesTransducin mediates signal transduction in a classical G protein-coupled receptor (GPCR) phototransduction cascade. Interactions of transducin with the receptor and the effector molecules had been extensively investigated and are currently defined at the atomic level. However, partners and functions of rod transducin α (Gαt1) and βγ (Gβ1γ1) outside the visual pathway are not well-understood. In particular, light-induced redistribution of rod transducin from the outer segment to the inner segment and synaptic terminal (IS/ST) allows Gαt1 and/or Gβ1γ1 to modulate synaptic transmission from rods to rod bipolar cells (RBCs). Protein-protein interactions underlying this modulation are largely unknown. We discuss known interactors of transducin in the rod IS/ST compartment and potential pathways leading to the synaptic effects of light-dispersed Gαt1 and Gβ1γ1. Furthermore, we show that a prominent non-GPCR guanine nucleotide exchange factor (GEF) and a chaperone of Gα subunits, resistance to inhibitors of cholinesterase 8A (Ric-8A) protein, is expressed throughout the retina including photoreceptor cells. Recent structures of Ric-8A alone and in complexes with Gα subunits have illuminated the structural underpinnings of the Ric-8A activities. We generated a mouse model with conditional knockout of Ric-8A in rods in order to begin defining the functional roles of the protein in rod photoreceptors and the retina. Our analysis suggests that Ric-8A is not an obligate chaperone of Gαt1. Further research is needed to investigate probable roles of Ric-8A as a GEF, trafficking chaperone, or a mediator of the synaptic effects of Gαt1.https://www.frontiersin.org/article/10.3389/fncel.2020.589494/fullretinaG proteinGPCRtransducinRic-8AGEF |
| spellingShingle | Dhiraj Srivastava Ravi P. Yadav Shivangi M. Inamdar Zhen Huang Maxim Sokolov Kimberly Boyd Nikolai O. Artemyev Nikolai O. Artemyev Transducin Partners Outside the Phototransduction Pathway Frontiers in Cellular Neuroscience retina G protein GPCR transducin Ric-8A GEF |
| title | Transducin Partners Outside the Phototransduction Pathway |
| title_full | Transducin Partners Outside the Phototransduction Pathway |
| title_fullStr | Transducin Partners Outside the Phototransduction Pathway |
| title_full_unstemmed | Transducin Partners Outside the Phototransduction Pathway |
| title_short | Transducin Partners Outside the Phototransduction Pathway |
| title_sort | transducin partners outside the phototransduction pathway |
| topic | retina G protein GPCR transducin Ric-8A GEF |
| url | https://www.frontiersin.org/article/10.3389/fncel.2020.589494/full |
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