Faculty and Research
Faculty by Name
Beth Burnside
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Beth Burnside
Vice Chancellor for Research and Chancellor's Professor of Cell and Developmental Biology*
*And Affiliate, Division of Neurobiology
Research Interests
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Our lab is investigating the roles of the actin cytoskeleton in the morphogenesis and survival of vertebrate retinal photoreceptors. These studies thus help us understand human vision and the prevention of blindness.
Current Projects
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Currently, we are studying two proteins associated with the elaborately polarized actin cytoskeleton of photoreceptor inner segments: the motor protein myosin 3A and the actin filament cross-linker fascin 2.
Class III myosins are unusual unconventional myosins. Although they have motor domains and bind actin like other myosins, they differ from all other myosins in having a kinase domain N-terminal to the motor domain. The presence of the kinase suggests that class III myosins play roles in cell signaling as well as in cell motility. Drosophila NINAC, the first class III myosin to be discovered, was initially identified as the defective gene responsible for causing photoreceptor degeneration in flies. Our lab cloned the first vertebrate homologues of NINAC to be identified, and showed that one of these homologues, Myo3A, is selectively expressed in vertebrate photoreceptors, where it is localized in microvillus-like processes that cup the base of the photopigment-bearing outer segment. We are now investigating the function of Myo3A by a variety of approaches, including heterologous expression in COS and HeLa cells, transgenic overexpression of Myo3A in Xenopus photoreceptors, and biochemical and molecular characterization of Myo3A kinase, motor, and tail domains.
Fascin 2 is a retinal-specific member of the fascin family of actin-binding proteins. Fascins are cross-linkers that bundle actin filaments. Fascin 2 mutation in humans results in autosomal dominant retinitis pigmentosa and macular dystrophy (Wada et al. (2001) IOVS 42:2395-2400, Wada et al. (2003) Ophth. Mol. Gen. 121:1613-1620), suggesting an important role for fascin 2 in photoreceptor survival. Currently we are analyzing the subcellular location of fascin 2 in photoreceptors using immunohistochemistry and GFP-tagged fascin 2 transgenes in Xenopus tadpole rods.
To investigate the functions of these proteins, we are using overexpression, antisense, and knockout approaches in Xenopus, zebrafish, and mouse. Xenopus transgenics have been generated in which the Xenopus opsin promoter drives photoreceptor-specific overexpression of a GFP-labeled myosin3A. Photoreceptors expressing the transgene develop large abnormal club-like processes containing actin filaments and terminal concentration of Myo3A, and later degenerate. Myo3A expressed in HeLa and COS cells concentrates at the distal tips of filapodia. Efforts are underway to knockout expression of Myo3A in vitro in cultured Xenopus eyecups, and in vivo in mouse by homologous recombination.
Selected Publications
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Retinomotor movements. B. Burnside and C. King-Smith (2006) In: Squire, L. (Ed.) New Encyclopedia of Neuroscience. Elsevier.
The retina-specific protein, fascin 2 is an actin crosslinker associated with actin bundles in photoreceptor inner segments and calycal processes. J. Lin-Jones and B. Burnside (2007). IOVS. 48(3): 1380-8.
The Kinetic Mechanism of Human Myosin IIIA. A.C. Dose, S. Ananthanarayanan, J.E. Moore, B. Burnside, C.M. Yengo (2006) J. Biol. Chem. 104 (3) 772-7.
A new compartment at stereocilia tips defined by spatial and temporal patterns of myosin IIIa expression. M.E. Schneider, A.C. Dose, F.T. Salles, W. Chang, F.L. Erickson, B. Burnside, B. Kachar (2006) J. Neuroscience. 26(40):10243-52.
Characterization of peripherin/rds and rom-1 transport in rod photoreceptors of transgenic and knockout animals. E.S. Lee, B. Burnside, J.G. Flannery. (2006) IOVS 47(5):2150-2160.
Myosin VI is required for structural integrity of the apical surface of sensory hair cells in zebrafish. C. Seiler, O. Ben-David, S. Sidi, O. Hendrich, A. Rusch, B. Burnside, K.B. Avraham, T. Nicolson (2004). Dev. Biol. 272(2):328-338.
Myosin III in photoreceptors: What does it do? A.C. Dose, J. Lin-Jones, and B. Burnside (2004) In: Photoreceptor Cell Bilogy and Inherited Retinal Degenerations (ed.) D.S. Williams, World Scientific Publishing, Singapore, 2004, pp. 351-370.
Myosin 3A transgene expression produces abnormal actin filament bundles in transgenic Xenopus laevis rod photoreceptors. J. Lin-Jones, E. Parker, M. Wu, A. Dose, and B. Burnside (2004) J. Cell. Sci. 117:5825-5834.
Disruption of Kinesin II Function Using a Dominant Negative-Acting Transgene in Xenopus laevis Rods Results in Photoreceptors Degenerations. J. Lin-Jones, E. Parker, M. Wu, B.E. Knox, and B. Burnside (2003) IOVS 44:3614-3621.
Localization of a Class III Myosin to Filopodia Tips in Transfected HeLa Cells Require an Actin-binding Site in its Tail Domain. F.L. Erickson, A.C. Corsa, A.C. Dose, and B. Burnside (2003) Mol. Biol. Cell. 14:1058-1073.
Myo3A, One of Two Class III Mysoin Genes Expressed in Vertebrate Retina, Is Localized to the Calycal Processes of Rod and Cone Photoreceptors and Is Expressed in the Sacculus. A.C. Dose, D. Hillman, C. Wong, L. Sohlberg, J. Lin-Jones, and B. Burnside (2003) Mol. Biol. Cell 14:4173-4180.
A Class III Myosin Expressed in the Retina Is a Potential Candidate for Bardet-Biedl Syndrome. A.C. Dose and B. Burnside (2002) Genomics 79:621-624.
Cloning and Chromosomal Localization of a Human Class III Myosin. A.C. Dose and B. Burnside (2000) Genomics 67:333-342.
Novel Myosin VI Isoform is Abundantly Expressed in Retina. J. Breckler, K. Au, J. Cheng, T. Hasson, and B. Burnside (2000) Exp. Eye Res. 70:121-134.
Photoreceptor Localization of the KIF3A and KIF3B Subunits of the Heterotrimeric Microtuble Motor Kinesin II in Vertebrate Retina. J.L. Whitehead, S.Y. Wang, L. Bost-Usinger, E. Hoang, K.A. Frazer, and B. Burnside (1999) Exp. Eye Res. 69:491-503.
Characterization of a novel C-kinesin (KIFC3) abundantly expressed in vertebrate retina and RPE. E. Hoang, L. Bost-Usinger, and B. Burnside (1999) Exp. Eye Res. 69:57-68.
Last Updated 2007-04-25