Organizer

Cendra Agulhon
Email
cendra.agulhon@u-paris.fr

Speaker

Location

Conference room R229
Campus Saint Germain des Prés de l'Université de Paris, 45 rue des Saints Pères, Paris 6e

Date

27 Jun 2022

Time

11 h 00 min - 12 h 00 min

Labels

INCC Seminar Series

Yif1B, a journey from serotonin receptor to cerebral development, by Justine Masson

Summary Yif1B, a journey from serotonin receptor to cerebral development

We identified Yif1B, a member of the ER/Golgi trafficking machinery as an interacting protein of the serotonin 5-HT1A receptor. We demonstrated that the inhibition of endogenous expression of Yif1B in primary neuron cultures prevented the addressing of 5-HT1AR to distal portions of the dendrites. We then showed that YIF1B is localized in the intermediate compartment between the endoplasmic reticulum (ER) and the Golgi apparatus and participates in the anterograde traffic from the ER to the cell membrane of the membrane- bound vesicular stomatitis virus G (VSV-G) protein in HeLa cells and in neurons. Its constitutive deletion in mouse neurons leads to Golgi apparatus disorganization and to a shorter travel of VSV-G through this compartment. Patients carrying mutations loss of function of YIF1B were identified. They displayed global developmental delay, motor delay, visual deficits with brain MRI evidence of ventricle enlargement, myelination alterations and cerebellar atrophy, and some these defects were observed in Yif1b knock out (KO) mice. In the CNS, Yif1b KO displayed neuronal reduction, altered myelination of the motor cortex, cerebellar atrophy, enlargement of the ventricles, and subcellular alterations of endoplasmic reticulum and Golgi apparatus compartments. Remarkably, although YIF1B was not detected in primary cilia, a tiny protusion of the cell membrane that is essential for cerebral development, biallelic YIF1B mutations caused primary cilia abnormalities in skin fibroblasts from both patients and Yif1b KO mice, and in ciliary architectural components in the Yif1b KO brain.

Short biography 

In 1998, Justine MASSON obtained a PhD in Michel Hamon’s unit (INSERM U288 – Faculté de Médecine Pitié-Salpêtrière, Paris) : she characterized an orphan transporter. Then she was a post-doc with Stephen Rayport and René Hen at Columbia University (New York – USA), generating a KO mice for the glutaminase type 1, an enzyme essential for glutamate « neurotransmitter » synthesis.

Since 2002, she has been a permanent researcher at CNRS in Michèle Darmon’s team (UMR U677 – Faculté de Médecine Pitié-Salpêtrière – Centre de Psychiatrie et neuroscience de Sainte-Anne – Université Paris Cité). She has recently joined Christine Métin’s team at the Institut du Fer à Moulin to focus on cortical development. Her research aims at characterizing the GLS1 KO and studying the regulation of 5-HT1A trafficking that leads to the identification of Yif1B.