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Kirk Mykytyn

Associate Professor

5034 Graves Hall
333 W. 10th Avenue
Columbus, OH 43210
Phone: (614) 292-4985
Email: mykytyn.1@osu.edu
 
Education:
 
PhD - University of Utah
Post Doctoral - University of Iowa

Research Interests

The research goals of my laboratory are to define the roles of primary cilia in cellular function and disease pathogenesis. Primary cilia are a class of cilia that are typically solitary, immotile appendages present on nearly every mammalian cell type. Primary cilia provide specialized sensory and signaling functions that are essential for normal development and cellular homeostasis. Disruption of ciliary structure or function causes a number of human diseases, collectively termed ciliopathies. Due to the ubiquity of cilia and their critical roles in numerous signaling pathways, ciliopathies present with a wide range of clinical features, including cystic kidney disease, retinal degeneration, obesity, skeletal defects, hypogonadism, anosmia, cognitive and social deficits, behavioral disturbances, and brain malformations. Yet, the precise function of most primary cilia and how they contribute to disease pathogenesis is largely unknown. This is especially true for primary cilia on neurons throughout the mammalian brain. Most neurons possess a primary cilium upon which certain G protein-coupled receptors (GPCRs) are specifically targeted, suggesting neuronal cilia sense neuromodulators in the extracellular space and provide specialized signaling. The importance of neuronal cilia is highlighted by the fact that ciliopathies are associated with numerous neurological defects. However, the roles of neuronal cilia in GPCR signaling and how they impact neuronal function are completely unknown.
We have discovered that the proteins associated with the human ciliopathy Bardet-Biedl syndrome (BBS) are required for proper trafficking of GPCRs into and out of neuronal cilia, suggesting disrupted ciliary GPCR trafficking is the basis for the neurological defects in BBS. We hypothesize that trafficking of ciliary GPCRs coordinates receptor signaling and disruption of ciliary trafficking alters the regulation of GPCR signaling and leads to physiological and behavioral abnormalities. Our goals are to define the mechanisms of ciliary GPCR trafficking, determine the effects of disrupted ciliary GPCR trafficking on signal transduction pathways, and determine the behavioral and physiological consequences. We have developed a unique set of resources for these studies, including; identification of novel ciliary GPCRs/signaling pathways, mouse models of disrupted ciliary GPCR trafficking that impact these pathways, and in vitro tools and systems for defining the mechanisms of ciliary GPCR trafficking and its impact on signaling. These resources will be used synergistically to understand the biology of cilia and ciliopathies.

Selected Publications

Koemeter-Cox A, Sherwood TW, Green JA, Steiner RA, Berbari NF, Yoder BK, Kauffman AS, Monsma PC, Brown A, Askwith CC, Mykytyn K (2014) Primary cilia enhance kisspeptin receptor signaling on gonadotropin-releasing hormone neurons. Proc Natl Acad Sci USA 111(28):10335-10340.
Jin X, Mohieldin AM, Muntean BS, Green JA, Shah JV, Mykytyn K, Nauli SM (2013) Cilioplasm is a cellular compartment for calcium signaling in response to mechanical and chemical stimuli. Cell Mol Life Sci 71(11):2165-2178.
Guadiana S, Semple-Rowland S, Daroszewski D, Madorsky I, Breunig J, Mykytyn K, Sarkisian M (2013) Arborization of dendrites by developing neocortical neurons is dependent on primary cilia and type 3 adenylyl cyclase. J Neurosci ​33(66):2626-2638.
Green JA, Gu C, Mykytyn K (2012) Heteromerization of ciliary G protein-coupled receptors in the mouse brain. PLoS ONE 7(9): e46304. doi:10:1371/journal.pone.0046304. PMCID: PMC3459911
Domire JS, Green JA, Lee KG, Johnson AD, Mykytyn K (2011) Dopamine receptor 1 localizes to neuronal cilia in a dynamic process that requires the Bardet-Biedl syndrome proteins. Cell Mol Life Sci 68(17):2951-2960. PMCID: PMC3368249
Green JA, Mykytyn K (2010) Neuronal ciliary signaling in homeostasis and disease. Cell Mol Life Sci 67(19):3287-3297. PMCID: PMC3349968
Domire JS, Mykytyn K (2009) Markers for neuronal cilia. Methods Cell Biol 91:111-121.
Berbari NF, Bishop GA, Lewis JS, Askwith CC, Mykytyn K (2008) Bardet-Biedl syndrome proteins are required for G protein-coupled receptor localization to neuronal cilia. Proc Natl Acad Sci USA 105(11):4242-4246. PMCID: PMC2393805
Berbari NF, Johnson AD, Lewis JS, Askwith CC, Mykytyn K (2008) Identification of ciliary localization sequences within the third intracellular loop of G protein-coupled receptors. Mol Biol Cell 19(4):1540-1547. PMCID: PMC2291422
Bishop GA, Berbari NF, Lewis JS, Mykytyn K (2007) Type III adenylyl cyclase localizes to primary cilia throughout the adult mouse brain. J Comp Neurol 505:562-571.
Mokrzan EM, Lewis JS, Mykytyn K (2007) Differences in renal tubule primary cilia length in a mouse model of Bardet-Biedl syndrome. Nephron Exp Nephrol 106:88-96.
Mykytyn K (2007) Clinical variability in ciliary disorders. Nature Genetics 39:818-819.
Berbari NF, Bishop GA, Askwith CC, Lewis JS, Mykytyn K (2007) Hippocampal neurons possess primary cilia in culture. J Neurosci Res 85:1095-1100. (cover illustration)
Mykytyn K, Sheffield VC (2004) Establishing a connection between cilia and Bardet-Biedl syndrome. Trends in Molec Med 10:106-109.
Nishimura DY, Fath M, Mullins RF, Searby C, Andrews M, Davis R, Andorf JL, Mykytyn K, Swiderski RE, Yang B, Carmi R, Stone EM, Sheffield VC (2004) Bbs2-null mice have neurosensory deficits, a defect in social dominance, and retinopathy associated with mislocalization of rhodopsin. Proc Natl Acad Sci USA 101:16588-16593.
Mykytyn K, Mullins RF, Andrews M, Chiang AP, Swiderski RE, Yang B, Braun T, Casavant T, Stone EM, Sheffield VC (2004) Bardet-Biedl syndrome type 4 (BBS4)-null mice implicate Bbs4 in flagella formation but not global cilia assembly. Proc Natl Acad Sci USA 101:8664-8669.
Mykytyn K, Nishimura DY, Searby CC, Beck G, Bugge K, Haines HL, Cornier AS, Cox GF, Fulton AB, Carmi R, Iannaccone A, Jacobson SG, Weleber RG, Wright AF, Riise R, Hennekam RCM, Luleci G, Berker-Karauzum S, Biesecker LG, Stone EM, Sheffield VC (2003) Evaluation of complex inheritance involving the most common Bardet-Biedl syndrome locus (BBS1). Am J Hum Genet 72:429-437.
Mykytyn K, Nishimura DY, Searby CC, Shastri M, Yen H, Beck JS, Braun T, Streb LM, Cornier AS, Cox GF, Fulton AB, Carmi R, Luleci G, Chandrasekharappa SC, Collins FS, Jacobson SG, Heckinlively JR, Weleber RG, Stone EM, Sheffield VC (2002) Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome. Nature Genetics 31:435-438.
Mykytyn K, Braun T, Carmi R, Haider NB, Searby CC, Shastri M, Beck G, Wright AF, Iannaccone A, Elbedour K, Riise R, Baldi A, Raas-Rothschild A, Gorman SW, Duhl DM, Jacobson SG, Casavant T, Stone EM, Sheffield VC (2001) Identification of the gene that, when mutated, causes the human obesity syndrome BBS4. Nature Genetics 28:188-191.​​