Author/Editor		Ma, EY; Lewis, A; Barabas, Peter; Stearns, G; Suzuki, S; Križaj, David; Brockerhoff, SE
Title		Loss of Pde6 reduces cell body Ca2[sup]+ transients within photoreceptors
Type		članek
Vol. and No.		Letnik 4
Publication year		2013
ISSN		2041-4889 - Cell death & disease
Language		eng
Abstract		Modulation of Ca2+ within cells is tightly regulated through complex and dynamic interactions between the plasma membrane and internal compartments. In this study, we exploit in vivo imaging strategies based on genetically encoded Ca2+ indicators to define changes in perikaryal Ca2+ concentration of intact photoreceptors. We developed double-transgenic zebrafish larvae expressing GCaMP3 in all cones and tdTomato in long-wavelength cones to test the hypothesis that photoreceptor degeneration induced by mutations in the phosphodiesterase-6 (Pde6) gene is driven by excessive [Ca2+]i levels within the cell body. Arguing against Ca2+ overload in Pde6 mutant photoreceptors, simultaneous analysis of cone photoreceptor morphology and Ca2+ fluxes revealed that degeneration of pde6cw59 mutant cones, which lack the cone-specific cGMP phosphodiesterase, is not associated with sustained increases in perikaryal [Ca2+]i. Analysis of [Ca2+]i in dissociated Pde6rd1mouse rods shows conservation of this finding across vertebrates. In vivo, transient and Pde6-independent Ca2+ elevations (flashes) were detected throughout the inner segment and the synapse. As the mutant cells proceeded to degenerate, these Ca2+ fluxes diminished. This study thus provides insight into Ca2+ dynamics in a common form of inherited blindness and uncovers a dramatic, light-independent modulation of [Ca2+]i that occurs in normal cones.
Keywords		calcium neurodegenerative disease photoreceptors kalcij nevrodegenerativna bolezen foto receptorji