The Olfactory System and Odorant Receptors

• Function of Olfactory System

  • Mamalian olfactory system recognizes and discriminates thousands of different odorant molecules.

  • Odor detection relies on specific receptors that bind to olfactory sensory neurons.

• Cell Types in Olfactory Epithelium

  • Olfactory Sensory Neurons (OSNs): Bipolar cells with cilia for odor detection.

  • Supporting (Sustentacular) Cells: Provide support to OSNs.

  • Basal Cells: Stem cells that generate new olfactory neurons.

Receptor Diversity

• Multigene Family for Odorant Receptors

  • Cloning revealed 18 members of a multigene family encoding seven transmembrane domain proteins.

  • Receptors likely associate uniquely with various odorants, allowing for the discrimination of complex smells.

  • Diversity predicted from the need to bind structurally distinct odorant molecules.

• Gene Classification

  • Odorant receptors are classified under a superfamily like neurotransmitter receptors.

  • Expressed mainly in the olfactory epithelium.

  • Functional implications suggest a few receptors may bind multiple odorants, similarly to color vision in photoreceptors.

Mechanism of Odor Detection

• Signal Transduction Pathway

  • Binding of an odorant to a receptor activates GTP-binding proteins, stimulating adenylyl cyclase to increase cyclic AMP (cAMP) levels.

  • Elevated cAMP leads to membrane depolarization, generating action potentials sent to the brain.

Experimental Approach to Study Odorant Receptors

• Gene Cloning Strategy

  • PCR amplification of olfactory epithelium tissue and cDNA libraries used to identify odorant receptor genes.

  • Restriction digestion of PCR products reveals multiple DNA species indicative of a multigene family.

• Analysis of cDNA Clones

  • Identified distinct cDNAs encoding proteins with conserved structural motifs and shared features with known receptor families.

  • Results suggest a novel family of olfactory-specific receptor proteins.

Expression Patterns and Genomic Insights

• Northern and Southern Blotting

  • Expression of the identified odorant receptors is specific to olfactory epithelium, with no detection in non-olfactory tissues such as brain or liver.

  • Genomic Southern blot analyses suggest hundreds of genes within the olfactory receptor family, indicating significant diversity.

Evolution and Functional Implications

• Evolution of Odorant Receptive Genes

  • The olfactory receptor gene family likely expanded over evolutionary time, allowing mammals to detect a wider array of odors.

• Odor Recognition Mechanism

  • The olfactory system might use a combinatorial coding scheme, where each receptor can bind various odorants leading to the activation of multiple receptors for odor discrimination.

  • This model highlights the significance of receptor diversity for complex odor recognition.