Liens transverses ENS de Lyon

Agenda de l'ENS de Lyon

Identification of a novel domain within the CIL regulates egress of IFITM3 from the Golgi and prevents its deleterious accumulation in this apparatus

jeu 30 sep 2021



Soutenance de Mme ZHONG Li sous la Direction de thèse de M. Andrea CIMARELLI

Langue(s) des interventions

Description générale

This thesis was carried out under the supervision of Dr Andrea Cimarelli within "host-pathogen interaction during lentiviral infection" team and was more specifically focused on the study of the biology of IFITM3, an important antiviral factor with a broad spectrum of viral inhibition. Starting from an initial observation carried out in the laboratory on a particular IFITM3 mutant, we have decided to study the role of the CIL in the passage and egress of the protein through the Golgi. The results gathered during my thesis work have allowed me to identify a particular region within the CIL of IFITM3 that regulates the normal egress of this protein through the Golgi. This step is very important as the abnormal retention of IFITM3 in this compartment leads to drastic changes and to a generalized defect in glycoprotein trafficking. These defects appear linked to the ability of Golgi-retained IFITM3 to inhibit fusion between v- and t-SNAREs bearing vesicles, in line with the more general inhibitory functions of IFITMs in membrane fusion.

Importantly, we also determine that the domain that regulates IFITM3 trafficking is conserved across other members of the dispanin A subfamily and functionally conserved in PRRT2, member of the dispanin B subfamily and involved in paroxysmal kinesigenic dyskinesia (PKD), the most common type of paroxysmal movement disorder.

Overall, these results identify a novel region important for the trafficking of IFITM3 through the Golgi and highlight the importance that tight regulation of this process may bear for the cell physiology.

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