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Le rôle des protéines courbant les membranes dans l’endocytose indépendante de la clathrine suivie par le récepteur de l’interleukine 2

Abstract : Endocytosis allows the uptake of elements from the extracellular fluid such as nutriments. This process takes place at the plasma membrane. The membrane curvatures play an important role in endocytosis for the production of initial invagination to form a pit that will be then separate from the plasma membrane and will go to the intracellular compartments. Several routes of endocytosis exist and can be classified depending on vesicles size formed, receptor mediated endocytosis or coat on vesicles. The well-known characterized endocytosis pathway is the clathrin mediated one. My lab is working on interleukin 2 receptor (IL-2R) entry. This receptor can enter either constitutively or upon induction by the ligand IL-2. Both uptake pathways are independent of clathrin. When I arrived in the lab, those pathways were still under characterization, in particular the factors inducing the membrane curvature. Their role should be important since IL-2R containing vesicles are coated free. A small interfering RNA screen performed before my phD, allowed to identify new candidates. The first part of my thesis was to verify the involvement of some of them in the IL-2R constitutive pathway and then to study their role in this pathway. Among them, 2 families of proteins were particularly interesting as they can curve membranes, phospholipases D and endophilins. The endophilin allowed the discovery of a new route called “Fast Endophilin Mediated Endocytosis” (FEME) in which it plays an essential role and which is used by numerous receptors that transmit signal. The FEME pathway shares several factors that are common with the IL-2 induced endocytosis pathway. Then, I conducted a work on the orchestration of endophilin and dynamin during the constitutive IL-2R endocytosis. Both factors are recruited at the end of the mechanism, to separate the vesicles from the plasma membrane. However, both proteins do not have the same orchestration. Our works show a distinct action of endophilin and dynamin in clathrin dependent and independent endocytosis.
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Laëtitia Bertot. Le rôle des protéines courbant les membranes dans l’endocytose indépendante de la clathrine suivie par le récepteur de l’interleukine 2. Biologie cellulaire. Université Paris-Saclay, 2016. Français. ⟨NNT : 2016SACLS570⟩. ⟨tel-01988742⟩

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