G _o α regulates olfactory adaptation by antagonizing G _q α-DAG signaling in Caenorhabditis elegans

Abstract

The heterotrimeric G protein Go is abundantly expressed in the mammalian nervous system and modulates neural activities in response to various ligands. However, G o's functions in living animals are less well understood. Here, we demonstrate that GOA-1 G o␣ has a fundamental role in olfactory adaptation in Caenorhabditis elegans. Impairment of GOA-1 G o␣ function and excessive activation of EGL-30 G q␣ cause a defect in adaptation to AWC-sensed odorants. These pathways antagonistically modulate olfactory adaptation in AWC chemosensory neurons. Wild-type animals treated with phorbol esters and double-mutant animals of diacylglycerol (DAG) kinases, dgk-3; dgk-1, also have a defect in adaptation, suggesting that elevated DAG signals disrupt normal adaptation. Constitutively active GOA-1 can suppress the adaptation defect of dgk-3; dgk-1 double mutants, whereas it fails to suppress the adaptation defect of animals with constitutively active EGL-30, implying that GOA-1 acts upstream of EGL-30 in olfactory adaptation. Our results suggest that down-regulation of EGL-30 -DAG signaling by GOA-1 underlies olfactory adaptation and plasticity of chemotaxis.chemotaxis ͉ G protein T he olfactory sensory system can endow animals with abilities to detect food sources and mates and, in some cases, to avoid harmful chemicals and predators. Sensitivity to an odor stimulus can be appropriately adjusted by previous experience, allowing the sensory system to adapt to changeable environments. In mammals, olfactory adaptation (habituation) is known to occur throughout the odorant sensory pathway; for example, olfactory receptor neurons (1), secondary interneurons (2), and primary and higher-order olfactory cortices (3). These adaptation mechanisms appear to allow animals to increase the range of concentrations of odor that can be sensed and to discriminate among multiple odors.The nematode Caenorhabditis elegans has only 302 neurons, and a variety of behaviors have been observed. Of these, olfactory behavior is relatively well studied. Volatile odorants are mainly sensed by five pairs of sensory neurons, AWA, AWB, AWC, ADL, and ASH (4-6), of which AWA and AWC chemosensory neurons mediate attraction behavior (4). In this response, olfactory adaptation has also been observed (7). Animals lacking OSM-9 TRPV channel (7, 8), EGL-4 cGMPdependent protein kinase (9) or animals overexpressing ODR-1 guanylyl cyclase (10) exhibited defects in olfactory adaptation to AWC-sensed odorants. By contrast, animals with mutated tax-6, which encodes calcineurin, exhibited hyperadaptation (11), suggesting that Ca 2ϩ and cGMP signaling cascades participate in olfactory adaptation. Moreover, ARR-1 arrestin (12), TBX-2 T-box transcription factor (13), and the Ras-MAPK pathway (14) are also known to act in olfactory adaptation, illustrating that olfactory adaptation in C. elegans is modulated by complicated mechanisms consisting of multiple signaling cascades and control of gene expression.In general, neural activities are modulated by many types of ligands th...

Ultraviolet-A triggers photoaging in model nematode Caenorhabditis elegans in a DAF-16 dependent pathway

“…Previous reports suggest that mutation in goa-1 has a negative impact on egg laying, locomotion, and other normal behaviors of the worm (Matsuki et al 2006). With the downstream activator dgk-1, GOA-1 will inhibit the egl-30-mediated DAG pathway (Matsuki et al 2006;Avery and You 2012). During the initial hours of exposure (2 h), egl-8, egl-30 were downregulated, and dgk-1, goa-1 were upregulated.…”

“…An ortholog of the heterotrimeric G protein alpha subunit Gq, egl-30, (Wang and Wadsworth 2002) and its downstream player, egl-8, (Ziegler et al 2009) in C. elegans plays a pivotal role in regulating pharyngeal pumping, egg laying and locomotion (Govorunova et al 2010). Previous reports suggest that mutation in goa-1 has a negative impact on egg laying, locomotion, and other normal behaviors of the worm (Matsuki et al 2006). With the downstream activator dgk-1, GOA-1 will inhibit the egl-30-mediated DAG pathway (Matsuki et al 2006;Avery and You 2012).…”

Generation and modulation of chemosensory behaviors in C. elegans

“…Intercellular mechanisms of plasticity In addition to intracellular mechanisms, intercellular communication also plays an important role in regulating adaptation behaviors [147,161] (Fig. 3b).…”

CASY-1, an ortholog of calsyntenins/alcadeins, is essential for learning in Caenorhabditis elegans

“…We have reported that the insulin/PI3K (phosphatidyl inositol 3-kinase) signaling pathway, Go (GOA-1) and Gq (EGL-30) pathway, and HEN-1, a secretory protein with an LDL motif, regulate salt chemotaxis learning (4,11,12). The insulin-like signaling pathway and HEN-1 also regulate temperature learning (5,12).…”