Yif1B, a journey from serotonin receptor to cerebral development

titleYif1B, a journey from serotonin receptor to cerebral development
start_date2022/06/27
schedule11h-12h
onlineno
location_infosalle de conférence R229
summaryWe 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.
responsiblesAgulhon

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submittedpublished2022/06/23 09:18 UTC
speakers
Masson
Event #183599 - latest update on 2022/06/23, created on 2022/06/23