Abstract
Rods and cones are photoreceptor neurons in the retina that are required for visual sensation in vertebrates, where proper protein localization and compartmentalization are critical for phototransduction and visual function. In human retinal diseases, improper protein transport to the outer segment (OS) or mislocalization of proteins to the inner segment (IS) could lead to impaired visual responses and photoreceptor cell degeneration, causing a loss of visual function. We showed involvement of an unconventional motor protein, MYO1C, in the proper localization of rhodopsin to the OS, where loss of MYO1C in a mammalian model caused mislocalization of rhodopsin to IS and cell bodies, leading to progressively severe retinal phenotypes. In this study, using modeling and docking analysis, we aimed to identify the protein–protein interaction sites between MYO1C and Rhodopsin to establish a hypothesis that a physical interaction between these proteins is necessary for the proper trafficking of rhodopsin and visual function.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Imanishi Y. Protein Sorting in Healthy and Diseased Photoreceptors. Annual Review of Vision Science. 2019;5(1):73–98.
Bales KL, Gross AK. Aberrant protein trafficking in retinal degenerations: The initial phase of retinal remodeling. Experimental Eye Research. 2016;150:71-80.
Jastrzebska B, Fotiadis D, Jang GF, Stenkamp RE, Engel A, Palczewski K. Functional and structural characterization of rhodopsin oligomers. J Biol Chem. 2006;281(17):11917–11922.
Jastrzebska B. GPCR: G protein complexes—the fundamental signaling assembly. Amino Acids. 2013;45(6):1303–1314.
Lobo GP, Ebke LA, Au A, Hagstrom SA. TULP1 Missense mutations induces the endoplasmic reticulum unfolded protein response stress complex (ER-UPR). Adv Exp Med Biol. 2016a;854:223–30.
Lobo GP, Au A, Kiser PD, Hagstrom SA. Involvement of Endoplasmic reticulum stress in tulp1 induced retinal degeneration. PLOS ONE. 2016b;11(3):e0151806–10.
Nemet I, Ropelewski P, Imanishi Y. (2015). Trafficking of GPCRs: rhodopsin trafficking and mistrafficking. Prog Mol Biol Transl Sci. 2015;132:39–71.
Orban T, Jastrzebska B, Palczewski K. Structural approaches to understanding retinal proteins needed for vision. Current Opinion in Cell Biology. 2014;27:32–43.
Solanki AK, et al. Loss of Motor Protein MYO1C Causes Rhodopsin Mislocalization and Results in Impaired Visual Function. Cells. 2021;10(6):1322.
Tamura K, Stecher G, Kumar S. MEGA11: Molecular Evolutionary Genetics Analysis Version 11 Abstract Molecular Biology and Evolution. 2021;38(7):3022–3027.
Hurwitz N, Schneidman-Duhovny D, Wolfson HJ. Memdock: an α-helical membrane protein docking algorithm. Bioinformatics. 2016;32(16):2444-2450.
van Zundert GCP, et al. The HADDOCK2.2 Web Server: User-Friendly Integrative Modeling of Biomolecular Complexes. J of Mol. Biol. 2016;428(4):720–725.
Sellers JR. Myosins: a diverse superfamily Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2000;1496(1):3–22.
Svitkina T. The Actin Cytoskeleton and Actin-Based Motility. Cold Spring Harbor Perspectives in Biology. 2018;10(1):a018267.
Mosby LS, et al. Myosin II Filament Dynamics in Actin Networks Revealed with Interferometric Scattering Microscopy. Biophysical Journal. 2020;118(8):1946–1957.
Hokanson DE, Laakso JM, Lin T, Sept D, Ostap EM. Myo1c Binds Phosphoinositides through a Putative Pleckstrin Homology Domain. Molecular Biology of the Cell. 2006;17(11):4856–4865.
Mazelova J, et al. Ciliary targeting motif VxPx directs assembly of a trafficking module through Arf4. The EMBO Journal. 2009;28(3):183–192.
Newport TD, Sansom MSP, Stansfeld PJ. The MemProtMD database: a resource for membrane-embedded protein structures and their lipid interactions. Nucleic Acids Research. 2019;47(D1) D390–D397.
Richard JJ, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596(7873):583–589.
Acknowledgments
This work was supported by the National Institute of Health—National Eye Institute (NIH-NEI) grants R21EY025034 and R01EY030889 to G.P.L. This project was also supported in part by a SCTR-NIH/NCATS grant (5UL1TR001450) and University of Minnesota Start-up funds to G.P.L.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this paper
Cite this paper
Lobo, G.P. et al. (2023). In Silico Prediction of MYO1C-Rhodopsin Interactions and Its Significance in Protein Localization and Visual Function. In: Ash, J.D., Pierce, E., Anderson, R.E., Bowes Rickman, C., Hollyfield, J.G., Grimm, C. (eds) Retinal Degenerative Diseases XIX. Advances in Experimental Medicine and Biology, vol 1415. Springer, Cham. https://doi.org/10.1007/978-3-031-27681-1_73
Download citation
DOI: https://doi.org/10.1007/978-3-031-27681-1_73
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-27680-4
Online ISBN: 978-3-031-27681-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)