Olfactory receptor cells are specialized neurons that have many long tapering cilia, as in the main olfactory organ of mammal, or many long microvilli, as in the vomeronasal olfactory organ of mammals. The distal parts of these cilia and microvilli line the interface between the external odorous environment and the luminal surface of the olfactory epithelium. Their length and number results in a large surface area that presumably increases the chance that an odor molecule will encounter a receptor cell. The distal parts of cilia and microvilli are likely to contain molecules involved in olfactory signal-transduction, analogous to outer segments of rods and cones in the retina. This is the working hypothesis of this proposal. We previously found that putative components of the olfactory cilia. Further ultrastructural studies are needed to determine whether other presumed transduction components, such as odor receptors and the olfactory cyclic nucleotide gated channel, are also present in the distal parts of the olfactory cilia, and whether the transduction cascades present in cilia are also present in vomeronasal microvilli. The overall aim of the proposal is to address these questions. Olfactory signal-transduction is thought to begin when odor molecules interact with members of a large family of specific odor receptors. This interaction leads to activation of a special G-protein, Golf, which in turn stimulates type III adenylyl cyclase. The elevated level of cAMP that results leads to the opening of cyclic nucleotide-gated ion channels, thereby depolarizing the cell. There is also evidence for an additional olfactory signal transduction cascade that involves phospholipase C and inositol trisphosphate (IP3)-gated cation channels. Both transduction mechanisms could operate independently or, alternatively, act in concert with each other. It is not precisely known if individual olfactory neurons utilize both of these transduction cascades. While biochemistry, physiology, and light microscopy can indicate cells and, to some degree, subcellular regions, where certain processes take place, ultrastructural/immunocytochemical studies under optimal preservational conditions can allow finer analyses of structures such as cilia and microvilli.. Such studies will ascertain unambiguously whether the distal parts of these structures contain all of the molecules that have thus far been implicated in olfactory signal-transduction. We will apply such studies 1) to show whether components of adenylyl cyclase/cAMP and phospholipase C/1P3 signaling cascades are present in the same or different subcellular compartments in rat olfactory epithelium, 2) to analyze the location of odor receptors int eh rat olfactory epithelium to determine whether olfactory cilia do indeed contain odor receptors, a long held but still undocumented supposition, 3) to assess whether components of adenylyl cyclase/cAMP and/or phospholipase C/IP3 signaling cascades occur in rat vomeronasal epithelium and, if so, whether they are present in the same or different subcellular compartments.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC002491-04
Application #
2634082
Study Section
Special Emphasis Panel (ZRG1-HAR (01))
Project Start
1995-01-01
Project End
1999-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60201
Carr, V M; Menco, B P; Yankova, M P et al. (2001) Odorants as cell-type specific activators of a heat shock response in the rat olfactory mucosa. J Comp Neurol 432:425-39
Menco, B P; Carr, V M; Ezeh, P I et al. (2001) Ultrastructural localization of G-proteins and the channel protein TRP2 to microvilli of rat vomeronasal receptor cells. J Comp Neurol 438:468-89
Matsuzaki, O; Bakin, R E; Cai, X et al. (1999) Localization of the olfactory cyclic nucleotide-gated channel subunit 1 in normal, embryonic and regenerating olfactory epithelium. Neuroscience 94:131-40
Menco, B P; Birrell, G B; Fuller, C M et al. (1998) Ultrastructural localization of amiloride-sensitive sodium channels and Na+,K(+)-ATPase in the rat's olfactory epithelial surface. Chem Senses 23:137-49
Menco, B P; Jackson, J E (1997) Cells resembling hair cells in developing rat olfactory and nasal respiratory epithelia. Tissue Cell 29:707-13
Menco, B P; Jackson, J E (1997) Neuron-like cells on the apical surface of the developing rat olfactory epithelium. Neurosci Lett 239:117-20
Menco, B P; Cunningham, A M; Qasba, P et al. (1997) Putative odour receptors localize in cilia of olfactory receptor cells in rat and mouse: a freeze-substitution ultrastructural study. J Neurocytol 26:297-312
Pixley, S K; Farbman, A I; Menco, B P (1997) Monoclonal antibody marker for olfactory sustentacular cell microvilli. Anat Rec 248:307-21
Menco, B P; Cunningham, A M; Qasba, P et al. (1997) Putative odour receptors localize in cilia of olfactory receptor cells in rat and mouse: a freeze-substitution ultrastructural study. J Neurocytol 26:691-706
Menco, B P; Jackson, J E (1997) A banded topography in the developing rat's olfactory epithelial surface. J Comp Neurol 388:293-306

Showing the most recent 10 out of 13 publications