Cilia- and Flagella-Associated Protein 69 Regulates Olfactory Transduction Kinetics in Mice

Abstract

Animals detect odorous chemicals through specialized olfactory sensory neurons (OSNs) that transduce odorants into neural electrical signals. We identified a novel and evolutionarily conserved protein, cilia-and flagella-associated protein 69 (CFAP69), in mice that regulates olfactory transduction kinetics. In the olfactory epithelium, CFAP69 is enriched in OSN cilia, where olfactory transduction occurs. Bioinformatic analysis suggests that a large portion of CFAP69 can form Armadillo-type ␣-helical repeats, which may mediate protein-protein interactions. OSNs lacking CFAP69, remarkably, displayed faster kinetics in both the on and off phases of electrophysiological responses at both the neuronal ensemble level as observed by electroolfactogram and the single-cell level as observed by single-cell suction pipette recordings. In single-cell analysis, OSNs lacking CFAP69 showed faster response integration and were able to fire APs more faithfully to repeated odor stimuli. Furthermore, both male and female mutant mice that specifically lack CFAP69 in OSNs exhibited attenuated performance in a buried food pellet test when a background of the same odor to the food pellet was present even though they should have better temporal resolution of coding olfactory stimulation at the peripheral. Therefore, the role of CFAP69 in the olfactory system seems to be to allow the olfactory transduction machinery to work at a precisely regulated range of response kinetics for robust olfactory behavior.

TMEM16B determines cholecystokinin sensitivity of intestinal vagal afferents of nodose neurons

“…Primary antibodies. Goat polyclonal anti-Ano1 (catalog sc-69343, lot E2714), which recognizes epitope amino acids 825-875 of human Ano1, is validated by Sun et al (73) in pulmonary artery protein lysates and several labs in other tissues (74)(75)(76)(77)(78)(79). It shows a band of approximately 114 kDa in Western blot.…”

Genetic causes of male infertility: snapshot on morphological abnormalities of the sperm flagellum

“…CFAP69 protein containing Armadillo-like helical repeats localizes to the midpiece of the sperm flagellum and in the mouse, Cfap69 gene invalidation was found to recapitulate the MMAF phenotype [17], confirming its implication in the processes of sperm flagellum structure and/or assembly. CFPA69 orthologous protein was found enriched in flagellar fraction of Chlamydomonas [21, 22] and interestingly, it is also enriched in cilia from mouse olfactory sensory neurons where it regulates the odour-response kinetics but has no apparent function in structure nor organization [23]. While, based on the mouse model phenotype, no ciliary structural defects of the olfactory neurons would be expected in CFAP69 mutated patients, further investigations of these patients should be performed to clearly rule out any olfactory functional symptoms.…”

Genomic approach to explore altered signaling networks of olfaction in response to diesel exhaust particles in mice

“…Cfap69 is mainly enriched in the cilia of OSNs, where olfactory receptors detect odorant molecules. Cfap69 facilitates the machinery of olfactory transduction to operate at an accurately regulated range of response kinetics to modulate olfactory behavior 28 . Accordingly, high expression of Cfap69 does not facilitate optimal sensory transduction.…”