Identification of the cellular processes altered in Ric-8B knockout mice by using transcriptome deep sequencing

• Grant number: 14/15495-8
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): December 01, 2014
• Effective date (End): May 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Bettina Malnic
• Grantee: Maíra Harume Nagai
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 17/00726-2 - Study of Ric-8B's function in mTOR activation by using an olfactory model, BE.EP.PD

Abstract

Animals can identify the chemical composition of the environment through the sense of smell. The odorants serve as cues to localize food and preys, avoid predators and comunicate with other animals. Odorant detection is mediated by millions of olfactory sensory neurons localized in the nasal cavity. Each olfactory neuron has a single dendrite that terminates in a knob with many cilia, where the olfactory receptors are found. Odorant binding to the olfactory receptors promotes the activation of the heterotrimeric G protein Golf. Once activated, the G±olf subunit exchanges GDP for GTP, then the GTP-bound G±olf dissociates from the G²³ complex and activates adenylyl cyclase III. The subsequent increase of the intracelular cAMP levels promotes the opening of cyclic nucleotide gated channels, leading to the influx of Na+ e Ca2+ and, in consequence, generation of action potentials. Previous findings from our laboratory showed the interaction of G±olf with RIC-8B, which could act as a regulator of the olfactory signaling. Adult mice coexpress RIC-8B and G±olf in the olfactory neurons and in the striatum of the brain. Moreover, RIC-8B is able to amplify olfactory signaling in a heterologous system. In vitro studies show that RIC-8B can couple to G±s and G±q, and acts as a guanine nucleotide exchange fator. In order to chacterize Ric-8B's function in olfaction, we generated a Ric-8B knockout mice line. We found that Ric-8B knockout mice are inviable, indicating that this protein is essential during the embryonic development. Ric-8B expression is restricted to the embryonic nervous system of wild type embryos and the knockout embryo exhibits cranial neural tube defects. This phenotype suggests a role for Ric-8B that differs from the one played in olfaction. Therefore, this study aims to elucidate the Ric-8B function during embryogenesis. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MACHADO, CLEITON F.; NAGAI, MARIA H.; LYRA, CASSANDRA S.; REIS-SILVA, THIAGO M.; MACHADO, ANDRE M.; GLEZER, ISAIAS; FELICIO, LUCIANO F.; MALNIC, BETTINA. Conditional Deletion of Ric-8b in Olfactory Sensory Neurons Leads to Olfactory Impairment. JOURNAL OF NEUROSCIENCE, v. 37, n. 50, p. 12202-12213, DEC 13 2017. (16/24471-0, 14/15495-8, 12/24640-6)

NAGAI, MAIRA H.; XAVIER, VICTOR P. S.; GUTIYAMA, LUCIANA M.; MACHADO, CLEITON F.; REIS, ALICE H.; DONNARD, ELISA R.; GALANTE, PEDRO A. F.; ABREU, JOSE G.; FESTUCCIA, WILLIAM T.; MALNIC, BETTINA. Depletion of Ric-8B leads to reduced mTORC2 activity. PLOS GENETICS, v. 16, n. 5, MAY 2020. (14/15495-8, 19/05166-0, 16/24471-0)