Goofy coordinates the acuity of olfactory signaling.
The basic scheme of odor perception and signaling from olfactory cilia to the brain is well understood. However, factors that affect olfactory acuity of an animal, the threshold sensitivity to odorants, are less well studied. Using signal sequence trap screening of a mouse olfactory epithelium cDNA library, we identified a novel molecule, Goofy, that is essential for olfactory acuity in mice. Goofy encodes an integral membrane protein with specific expression in the olfactory and vomeronasal sensory neurons and predominant localization to the Golgi compartment. Goofy-deficient mice display aberrant olfactory phenotypes, including the impaired trafficking of adenylyl cyclase III, stunted olfactory cilia, and a higher threshold for physiological and behavioral responses to odorants. In addition, the expression of dominant-negative form of cAMP-dependent protein kinase results in shortening of olfactory cilia, implying a possible mechanistic link between cAMP and ciliogenesis in the olfactory sensory neurons. These results demonstrate that Goofy plays an important role in establishing the acuity of olfactory sensory signaling.
RIKEN Brain Science Institute, Saitama 351-0198, Japan.
Tomomi
T
Kaneko-Goto
Yuki
Y
Sato
Sayako
S
Katada
Emi
E
Kinameri
Sei-ichi
S
Yoshihara
Atsushi
A
Nishiyori
Mitsuhiro
M
Kimura
Hiroko
H
Fujita
Kazushige
K
Touhara
Randall R
RR
Reed
Yoshihiro
Y
Yoshihara
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D003001:Cloning, Molecular; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics / Q000378:metabolism; D005071:Evoked Potentials / Q000235:genetics; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009812:Odorants; D051842:Olfactory Marker Protein / Q000235:genetics / Q000378:metabolism; D009833:Olfactory Pathways / Q000033:anatomy & histology / Q000378:metabolism*; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D012333:RNA, Messenger; D018035:Receptors, Odorant / Q000235:genetics / Q000378:metabolism; D017421:Sequence Analysis; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D054815:Cyclic Nucleotide-Gated Cation Channels; C489921:Ebf1 protein, mouse; C584162:Goofy protein, mouse; D008164:Luminescent Proteins; D051842:Olfactory Marker Protein; C497598:Omp protein, mouse; D012333:RNA, Messenger; D018035:Receptors, Odorant; D015534:Trans-Activators; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; C421784:adenylate cyclase 3