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Theses

Mécanismes du transfert intercellulaire des homéoprotéines

Abstract : Homeoproteins belong to a family of transcription factors which all share a common DNA binding domain, the homeodomain. Beside their action as transcription factors, homeoproteins are also able to be transferred between cells by unconventional means. The two consecutive steps of this intercellular transfer (secretion then internalisation) require sequences located in the homeodomain. Thanks to studies previously lead by our laboratory, we know that subcellular localisation of ENGRAILED-2 (EN-2) homeoprotein is a crucial step in its subsequent secretion. On this basis, we showed that EN-2 interacts directly with a certain subtype of phospholipids, phosphoinositides [e.g. PI(4,5)P2]. Then, we demonstrated than these lipids are involved in the association of EN-2 protein with membraneous compartments within the cell. PI(4,5)P2 located in the inner leaflet of the plasma membrane are also involved in the direct translocation of EN-2 across plasma membrane. This work is also focused on the role of proteoglycans, and more precisely syndecans, in EN-2 cell surface accumulation after both secretion and internalisation. At last, we also established the implication of EN-2 interaction domain with PBX in EN-2 intercellular transfer.
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https://tel.archives-ouvertes.fr/tel-01264533
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Submitted on : Friday, January 29, 2016 - 1:03:51 PM
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Thibault Lin. Mécanismes du transfert intercellulaire des homéoprotéines. Biologie cellulaire. Université Pierre et Marie Curie - Paris VI, 2015. Français. ⟨NNT : 2015PA066346⟩. ⟨tel-01264533⟩

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