Bidirectional transfer of Engrailed homeoprotein across the plasma membrane requires PIP2

Autor: Julie Miralvès, Alain Joliot, Irène Amblard, Isabelle Queguiner, Isabel D. Alves, Edmond Dupont
Přispěvatelé: Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Journal of Cell Science
Journal of Cell Science, Company of Biologists, 2020, ⟨10.1101/2020.01.21.913566⟩
ISSN: 0021-9533
1477-9137
Popis: 1.AbstractHomeoproteins are a class of transcription factors sharing the unexpected property of intercellular trafficking. It confers to homeoproteins a paracrine mode of action, shown to exert a wide range of physiological functions, during development and in the adult. Internalization and secretion, the two steps of intercellular transfer, rely on unconventional mechanisms but the cellular mechanisms at stake still need to be fully characterized. Thanks to the design of new quantitative and sensitive assays dedicated to the study of homeoprotein transfer in cell culture, we demonstrate a core role of the phosphoinositides PIP2 together with cholesterol in the translocation of Engrailed2 (EN2) homeoprotein across the plasma membrane. Both secretion and internalization are regulated according to PIP2 levels, challenged by drug or enzymatic treatments. In addition, EN2 specifically interacts with PIP2 and the reduced affinity of a paracrine deficient mutant of EN2 supports a role of PIP2 in homeoprotein physiological function. We propose that the two ways plasma membrane translocation steps accounting for homeoprotein secretion and internalization respectively are parts of a common process.Summary StatementDeciphering the mechanism of homeoprotein intercellular trafficking
Databáze: OpenAIRE