Like most animals, insects rely on olfaction to find food and mates and avoid noxious chemicals and predators. Most insect olfactory sensory neurons (OSNs) express an odorant-specific odorant receptor (OR) along with Orco, the olfactory co-receptor. Orco binds ORs and permits their trafficking to the dendrites of antennal OSNs, where together, they are suggested to form heteromeric, ligand-gated, non-selective cation channels. Within Orco's second intracellular loop, there is an especially well-conserved sequence strongly predicted to be a calmodulin (CaM) binding site (CBS). In this study, I explored the relationship between Orco and CaM \emph{in vivo} in the olfactory neurons of Drosophila melanogaster. I first found OSN-specific knock-down of CaM at the onset of OSN development disrupts the spontaneous firing of OSNs and reduces Orco trafficking to the ciliated dendrites of OSNs. I then generated a series of Orco CBS mutant proteins and found that none of them rescue the Orco-null $Orco^1$ mutant phenotype, which is characterized by an OR protein trafficking defect that blocks spontaneous and odorant-evoked OSN activity. In contrast to an identically constructed wild-type form of Orco that does rescue the $Orco^1$ phenotype, all the Orco CBS mutants remain stuck in the OSN soma. Last, I found CaM's modulation of OR trafficking is activity-dependent. Knock-down of CaM in OSNs after OR expression is well-established has little effect on olfactory responsiveness alone. When combined with an extended exposure to odorant, however, this late-onset CaM knock-down significantly reduces both olfactory sensitivity and the trafficking of Orco only to the ciliated dendrites of OSNs that respond to the exposed odorant. Therefore, I propose a model in which the CaM/Orco interaction allows insect OSNs to maintain appropriate dendritic levels of OR regardless of environmental odorant concentrations.
곤충은 후각으로 음식, 숙주, 그리고 위험을 감지한다. 곤충 후각신경세포 안에는 각 신경세포가 어떠한 리간드에 반응할 것인지 결정하는 후각수용체, 그리고 후각수용체의 수송 및 기능에 필수적인 후각보조수용체가 존재한다. 다양한 종의 곤충 후각보조수용체 서열을 비교해 보면, 칼슘 센서 단백질인 칼모듈린의 결합자리로 강하게 추정되는 서열이 거의 완벽히 보존되어 있음을 알 수 있다. 본 연구는 노랑초파리 후각신경세포 내의 칼모듈린 발현 조절과 칼모듈린 결합자리가 변이된 후각보조수용체 발현을 통해 칼모듈린이 후각보조수용체와 후각수용체의 수송에 필수적이라는 것을 밝혔다. 또한 주변 환경에 냄새물질이 많을 때 이러한 수송이 더 활성화 된다는 것도 발견하였다. 특정 냄새가 강하게 집중된 환경에서 칼모듈린을 하향조절 시키면 전기 생리학적 방법으로 측정한 후각반응이 현저히 떨어지고, 후각신경세포의 수상돌기로 수송된 후각보조수용체의 양이 줄어든다는 것을 확인하였다.
