Maxim Sokolov, PhD
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PO Box 9193
WVU Eye Institute
Morgantown, WV 26506
My laboratory studies G protein mediated signaling in the retina photoreceptors, highly specialized neurons responsible for acquisition of visual information. My research program addresses the fundamental, yet poorly understood mechanisms that govern synthesis, delivery, and degradation of signaling proteins in neurons. Our multi-tiered experimental approach offers an exciting opportunity to master a variety of techniques including antibody-based protein recognition, confocal fluorescence microscopy, real-time PCR and gene arrays, mass spectrometry, and transgenics.
Phosducin and Its Role in Rod Photoreceptors
Phosducin (Pdc) is a major phosphoprotein of retinal photoreceptors that interacts with the beta-gamma dimers of heterotrimeric G proteins in its dephosphorylated state. In the retinas of living animals, phosphorylation status of Pdc is tightly controlled by light; thus, it was proposed that Pdc acts as a light-dependent regulator of various G protein-mediated functions including visual signal transduction and synaptic transmission. Physiological roles of Pdc in photoreceptors, however, remained largely hypothetical until the generation of Pdc knockout mice. The analysis of this mutants revealed that Pdc regulates subcellular localization of visual G protein, transducin (Sokolov et. al., 2004), a cellular mechanism of rod adaptation to bright ambient illumination (Sokolov et. al., 2002). It was also found that deletion of phosducin gene cause rods to produce less transducin and have significantly reduced sensitivity of their light responses (Krispel et. al., 2007). Our next goal is to elucidate how Pdc regulates expression and subcellular localization of transducin in order to provide important insights into the general principals of G protein regulation in retinal photoreceptors. Another direction of our studies is to determine mechanisms and physiological role of light-dependent Pdc phosphorylation. Our most recent inquiries into this phenomenon have provided important information on regulation of two principal light-regulated phosphorylation sites of Pdc, Ser 54 and 71, inliving animals (Song et al., 2007). We have found distinct compartment-specific phosphorylation of Ser 54 and Ser 71 and proposed that Pdc has different functions in different cellular compartments of rods. To elucidate these functions, we have expressed mutant Pdc lacking Ser 54 and Ser 71 in rods of mice using transgenic approach, and begun characterization of these mutants.
Translocation of Signaling Proteins in Photoreceptors
Our laboratory also studies light-evoked responses of rod photoreceptors that include translocation of signaling proteins between cellular compartments of these neurons (Sokolov et. al., 2002; Strissel et. al., 2006; Lobanova et. al., 2007). We utilize the original retinal microdissection technique, which enables protein analysis within the distinct subcellular compartments of photoreceptor cells (Sokolov et. al., 2002; Song et. al., 2007). Our goal is to further develop this technique by coupling tissue microdissection and MS-based protein identification, and to elucidate the roles of signal-protein translocation in photoreceptor function.
- Wright ZC, SIngh RK, Alpino R, Goldberg AF, Sokolov M, Ramamurthy V. ARL3 regulates trafficking of prenylated phototransduction proteins to the rod outer segment. Hum Mol Genet (2016) [Epub ahead of print].
- Sinha S, Belcastro M, Datta P, Seo S, Sokolov M. Essential role of the chaperonin CCT in rod outer segment biogenesis. Invest Ophthalmol Vis Sci (2014) 55(6): 3775-85. PMCID: PMC4062400.
- Gao X, Sinha S, Belcastro M, Woodard C, Ramamurthy V, Stoilov P, Sokolov M. Splice isoforms of phosducin-like protein control the expression of heterotrimeric G proteins. J Biol Chem (2013 Sep 6); 288(36):25760-8.
- Sinha S, Majumder A, Belcastro M, Sokolov M, Artemyev NO. Expression and subcellular distribution of UNC119a, a protein partner of transducin α subunit in rod photoreceptors. Cell Signal (2013 Jan) 25(1): 341-8. doi: 10.1016/j.cellsig.2012.10.005.
- Belcastro M, Song H, Sinha S, Song C, Mathers PH, Sokolov M. Phosphorylation of phosducin accelerates rod recovery from transducin translocation. Invest Ophthalmol Vis Sci (2012 May 1) 53(6): 3084-91. doi: 10.1167/iovs.11-8798.
- Yang J, Wang L, Song H, Sokolov M. Current understanding of usher syndrome type II. Front Biosci (2012 Jan 1) 17:1165-83.
- Posokhova E, Song H, Belcastro M, Higgins L, Bigley LR, Michaud NA, Martemyanov KA, Sokolov M. Disruption of the chaperonin containing TCP-1 function affects protein networks essential for Rod outer segment morphogenesis and survival. Mol Cell Proteomics. 2010 Sep 17.
- Edrington TC, Sokolov M, Boesze-Battaglia K. Peripherin/rds co-distributes with putative binding partners in basal rod outer segment disks. Exp Eye Res (2011) 92(5):439-42.