TY - JOUR
T1 - Energy requirements of odor transduction in the chemosensory cilia of olfactory sensory neurons rely on oxidative phosphorylation and glycolytic processing of extracellular glucose
AU - Villar, Pablo S.
AU - Delgado, Ricardo
AU - Vergara, Cecilia
AU - Reyes, Juan G.
AU - Bacigalupo, Juan
N1 - Funding Information:
This work was supported by Fondo Nacional de Cienciay Tecnolog?a 1140520. We thank Dr. Carolina Gonz?lez for help on image analysis and Daniela Villalobos for help in the glucose measurements. We are especially grateful to Dr. Ricardo C. Araneda for allowing us to perform some of the experiments in his laboratory during the revision of this manuscript.
Publisher Copyright:
© 2017 the authors.
PY - 2017/6/7
Y1 - 2017/6/7
N2 - The mechanisms that power the physiological events occurring in cilia, flagella, and microvilli are of fundamental importance for the functions of these important and ubicuous organelles. The olfactory epithelium is mostly populated by ciliated olfactory sensory neurons (OSNs) and surrounding sustentacular cells (SCs) with apical microvilli. The only OSN dendrite extends to the surface forming a knob projecting several chemosensory cilia of ~50 ×0.2 μm, devoid of inner membranes embedded in a mucus layer. Upon odorant binding, odor receptors couple to G-protein activating adenylyl cyclase, producing cAMP. cAMP opens cyclic nucleotide-gated channels allowing a Ca2+ influx that opens Ca2+-activated Cl- channels, generating the receptor potential. Many enzymes are activated in chemotransduction to hydrolyze ATP. The knob contains approximately two mitochondria; assuming that the cilia ATP is 1 mM and diffuses along it at ~10 μm in 500 ms, ATP from the knob mitochondria may not fulfill the demands of transduction over the full length of the cilium, which suggests an additional ATP source. We measured millimolar glucose in rat mucus; we detected glucose transporter GLUT3 in rat and toad (Caudiverbera caudiverbera) OSN cilia, SC microvilli, and glycolytic enzymes in rat cilia. We also found that the cilia and knob can incorporate and accumulate 2-deoxyglucose (glucose analog), but not when blocking GLUT. Glucose removal and the inhibition of glycolysis or oxidative phospholylation impaired the odor response. This evidence strongly suggests that glycolysis in the cilia and knob oxidative phosphorylation together fuel chemotransduction.
AB - The mechanisms that power the physiological events occurring in cilia, flagella, and microvilli are of fundamental importance for the functions of these important and ubicuous organelles. The olfactory epithelium is mostly populated by ciliated olfactory sensory neurons (OSNs) and surrounding sustentacular cells (SCs) with apical microvilli. The only OSN dendrite extends to the surface forming a knob projecting several chemosensory cilia of ~50 ×0.2 μm, devoid of inner membranes embedded in a mucus layer. Upon odorant binding, odor receptors couple to G-protein activating adenylyl cyclase, producing cAMP. cAMP opens cyclic nucleotide-gated channels allowing a Ca2+ influx that opens Ca2+-activated Cl- channels, generating the receptor potential. Many enzymes are activated in chemotransduction to hydrolyze ATP. The knob contains approximately two mitochondria; assuming that the cilia ATP is 1 mM and diffuses along it at ~10 μm in 500 ms, ATP from the knob mitochondria may not fulfill the demands of transduction over the full length of the cilium, which suggests an additional ATP source. We measured millimolar glucose in rat mucus; we detected glucose transporter GLUT3 in rat and toad (Caudiverbera caudiverbera) OSN cilia, SC microvilli, and glycolytic enzymes in rat cilia. We also found that the cilia and knob can incorporate and accumulate 2-deoxyglucose (glucose analog), but not when blocking GLUT. Glucose removal and the inhibition of glycolysis or oxidative phospholylation impaired the odor response. This evidence strongly suggests that glycolysis in the cilia and knob oxidative phosphorylation together fuel chemotransduction.
KW - Chemotransduction
KW - Glucose transport
KW - Glycolysis
KW - Mucus
KW - Olfactory cilia
KW - Oxidative phosphorylation
UR - http://www.scopus.com/inward/record.url?scp=85020483015&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2640-16.2017
DO - 10.1523/JNEUROSCI.2640-16.2017
M3 - Article
C2 - 28500222
AN - SCOPUS:85020483015
VL - 37
SP - 5736
EP - 5743
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 23
ER -