The microtubule-binding protein CLIP-170 coordinates mDia1 and actin reorganization during CR3-mediated phagocytosis

Microtubule dynamics are modulated by regulatory proteins that bind to their plus ends (+TIPs [plus end tracking proteins]), such as cytoplasmic linker protein 170 (CLIP-170) or end-binding protein 1 (EB1). We investigated the role of +TIPs during phagocytosis in macrophages. Using RNA interference and dominant-negative approaches, we show that CLIP-170 is specifically required for efficient phagocytosis triggered by αMβ2 integrin/complement receptor activation. This property is not observed for EB1 and EB3. Accordingly, whereas CLIP-170 is dynamically enriched at the site of phagocytosis, EB1 is not. Furthermore, we observe that CLIP-170 controls the recruitment of the formin mDia1, an actin-nucleating protein, at the onset of phagocytosis and thereby controls actin polymerization events that are essential for phagocytosis. CLIP-170 directly interacts with the formin homology 2 domain of mDia1. The interaction between CLIP-170 and mDia1 is negatively regulated during αMβ2-mediated phagocytosis. Our results unravel a new microtubule/actin cooperation that involves CLIP-170 and mDia1 and that functions downstream of αMβ2 integrins

Entretien

Annette Gonnin-Bolo – Vous avez travaillé sur de nombreux objets de recherche tout au long de votre vie professionnelle, à quel moment la notion d’accompagnement a-t-elle émergé ? Comment êtes-vous entré progressivement dans des problématiques d’accompagnement et sous quel angle ? Jean-Pierre Boutinet – Plusieurs générations d’objets de recherche m’ont intéressé et je pourrais les unifier autour de la même thématique « l’acteur et son action », « l’acteur au regard de son action ». De l’acteu..

Viability and stress protection of chronic lymphoid leukemia cells involves overactivation of mitochondrial phosphoSTAT3Ser 727

International audienceChronic lymphoid leukemia (CLL) is characterized by the accumulation of functionally defective CD5-positive B lymphocytes. The clinical course of CLL is highly variable, ranging from a long-lasting indolent disease to an unpredictable and rapidly progressing leukemia requiring treatment. It is thus important to identify novel factors that reflect disease progression or contribute to its assessment. Here, we report on a novel STAT3-mediated pathway that characterizes CLL B cells-extended viability and oxidative stress control. We observed that leukemic but not normal B cells from CLL patients exhibit constitutive activation of an atypical form of the STAT3 signaling factor, phosphorylated on serine 727 (Ser 727) in the absence of detectable canonical tyrosine 705 (Tyr 705)-dependent activation in vivo. The Ser 727 -phosphorylated STAT3 molecule (pSTAT3Ser 727) is localized to the mitochondria and associates with complex I of the respiratory chain. This pSer 727 modification is further controlled by glutathione-dependent antioxidant pathway(s) that mediate stromal protection of the leukemic B cells and regulate their viability. Importantly, pSTAT3Ser 727 , but neither Tyr705-phosphorylated STAT3 nor total STAT3, levels correlate with prolonged in vivo CLL B cells survival. Furthermore, STAT3 activity contributes to the resistance to apoptosis of CLL, but not normal B cells, in vitro. These data reveal that mitochondrial (Mt) pSTAT3Ser 727 overactivity is part of the antioxidant defense pathway of CLL B cells that regulates their viability. Mt pSTAT3Ser 727 appears to be a newly identified cell-protective signal involved in CLL cells survival. Targeting pSTAT3Ser 727 could be a promising new therapeutic approach

Autour du mot « Professionnalité »

Mathey-Pierre Catherine, Bourdoncle Raymond. Autour du mot « Professionnalité ». In: Recherche & Formation, N°19, 1995. Recherches sur les institutions et pratiques de formation. pp. 137-148

« Recherche » et « Développement professionnel »

Bourdoncle Raymond, Mathey-Pierre Catherine. « Recherche » et « Développement professionnel ». In: Recherche & Formation, N°17, 1994. Recherche et développement professionnel. pp. 141-154