A Drosophila Nonvisual Arrestin Is Required for the Maintenance of Olfactory Sensitivity

Abstract

Nonvisual arrestins are a family of multifunctional adaptor molecules that regulate the activities of diverse families of receptors including G protein-coupled receptors, frizzled, and transforming growth factor-beta receptors. These activities indicate broad roles in both physiology and development for nonvisual arrestins. Drosophila melanogaster has a single nonvisual arrestin, kurtz, which is found at high levels within the adult olfactory receptor neurons (ORNs), suggesting a role for this gene in modulating olfactory sensitivity. Using heat-induced expression of a krz cDNA through development, we rescued krz(1) lethality. The resulting adults lacked detectable levels of krz in the olfactory system. The rescued krz(1) homozygotes have an incompletely penetrant antennal structural defect that was completely rescued by the neural expression of a krz cDNA. The krz(1) loss-of-function adults without visible antennal defects displayed diminished behavioral responsiveness to both aversive and attractive odors and also demonstrated reduced olfactory receptor potentials. Both the behavioral and electrophysiological phenotypes were rescued by the targeted expression of the krz cDNA within postdevelopmental ORNs. Thus, krz is required within the nervous system for antennal development and is required later in the ORNs for the maintenance of olfactory sensitivity in Drosophila. The reduced receptor potentials in krz(1) antenna indicate that nonvisual arrestins are required for the early odor-induced signaling events within the ORNs.

Exploratory Activity in Drosophila Requires thekurtzNonvisual Arrestin

“…However, the highest level of KRZ expression was within the neuropil of the central nervous system (CNS) ( Figure 1A). Previously, KRZ was also detected at high levels in the sensory systems of the second and third antennal segments (Ge et al 2006). The second antennal segment contains Johnston's organ, the primary auditory organ for adult Drosophila, while the third antennal segment is the primary olfactory organ of the fly (Miller 1950).…”

“…The krz 1 lethal phase is protracted, occurring throughout embryonic and larval development. To surmount this problem, krz 1 homozygotes were rescued to adulthood by using heat-induced Gal4 to drive the expression of a krz cDNA ubiquitously during development (Ge et al 2006). The genotypes of these rescued homozygotes are listed in Table 1.…”

“…These same conditions were used to raise all control flies for experiments that included the krz 1 homozygotes. The OR83bGal4; krz 1 rescued flies were generated as stated in Ge et al (2006), using the second chromosome OR83bGal4 driver (Kalidas and Smith 2002).…”

“…Immunohistochemistry and in situ hybridization: The antikrz polyclonal antibodies were prepared as described in Ge et al (2006). The immunohistochemistry on paraffin sections and in situ hybridization on cryosection experiments were performed largely as previously described with a few modifications (Roman et al 1998).…”

Regulation of Toll Signaling and Inflammation by β-Arrestin and the SUMO Protease Ulp1

“…More recently, our knowledge of their signaling functions has dramatically broadened to involve a wide variety of signaling pathways and modes of regulation (Kovacs et al 2009). The Drosophila genome encodes a single ortholog of b-arrestins, Kurtz (Krz) (Roman et al 2000), which has been implicated in the regulation of GPCR signaling, as well as Notch, Hedgehog, receptor tyrosine kinase, and Toll pathways (Mukherjee et al 2005;Ge et al 2006;Tipping et al 2010;Molnar et al 2011;Li et al 2012).…”