Lipid dynamics of olfactory neuron cilia: Implications for olfactory receptor functionality

• Grant number: 24/11845-6
• Support Opportunities: Scholarships in Brazil - Support Program for Fixating Young Doctors
• Effective date (Start): September 01, 2024
• Effective date (End): August 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Acordo de Cooperação: CNPq
• Principal Investigator: Bettina Malnic
• Grantee: André Machado Xavier
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 24/01998-0 - Lipid dynamics of olfactory neuron cilia: Implications for olfactory receptor functionality, AP.R

Abstract

The olfactory system plays a fundamental role in the interaction of living organisms with the surrounding environment, influencing aspects ranging from survival to sociability. The cells responsible for this interaction are Olfactory Sensory Neurons (OSNs), specialized neurons located in the Olfactory Epithelium (OE), which play a central role in odor detection. OSNs express a single olfactory receptor (OR) gene each, and are used combinatorially to identify and discriminate different odorants. Interestingly, it is in the cilia that olfactory receptors responsible for recognizing odorant molecules are located, along with their entire signaling machinery, including G±olf, ACIII, and the cyclic nucleotide-gated (CNG) channel. Olfactory cilia are complex structures that present a (9 x 2 x 2) microtubular axoneme configuration, commonly found in mobile cilia, but the absence of the molecular motor dynein confers upon them a status of non-mobile cilia. As important as genes and proteins in the olfaction, comprehending the role of lipids in the olfactory epithelium is vital to unraveling the mechanisms underlying odor detection. Lipids play essential roles in the structure and function of olfactory cells, yet despite their importance, there is a significant gap in knowledge regarding the specific lipid composition of olfactory cilia. Few groups have explored the lipid diversity of the olfactory epithelium in the past, and the technology used in these studies is relatively outdated, limiting our ability to fully understand the role of lipids in this context. Therefore, it is imperative to invest in updated research and advanced technologies to elucidate the role of lipids in olfactory cilia. In this context, this project proposes to investigate the lipid composition of olfactory neuron cilia, identify lipid microdomains and their relative distribution to olfactory receptors, and finally, explore the influence of the lipid microenvironment on OR functionality, contributing to a deeper understanding of the mechanisms underlying olfactory perception. This understanding not only contributes to the advancement of fundamental knowledge about olfactory physiology but may also have practical implications in the development of therapeutic strategies for olfaction-related disorders. (AU)