12 research outputs found
EHD2 is a mechanotransducer connecting caveolae dynamics with gene transcription
Caveolae are small invaginated pits that function as dynamic mechanosensors to buffer tension variations at the plasma membrane. Here we show that under mechanical stress, the EHD2 ATPase is rapidly released from caveolae, SUMOylated, and translocated to the nucleus, where it regulates the transcription of several genes including those coding for caveolae constituents. We also found that EHD2 is required to maintain the caveolae reservoir at the plasma membrane during the variations of membrane tension induced by mechanical stress. Metal-replica electron microscopy of breast cancer cells lacking EHD2 revealed a complete absence of caveolae and a lack of gene regulation under mechanical stress. Expressing EHD2 was sufficient to restore both functions in these cells. Our findings therefore define EHD2 as a central player in mechanotransduction connecting the disassembly of the caveolae reservoir with the regulation of gene transcription under mechanical stress
Endocytose sans clathrine
LâintĂ©rĂȘt portĂ© Ă lâĂ©tude des mĂ©canismes dâendocytose nâa jamais faibli tant ce phĂ©nomĂšne tient une place essentielle dans le fonctionnement cellulaire. La croissance, lâadhĂ©sion et la diffĂ©renciation cellulaires, la rĂ©gulation de la signalisation induite par les rĂ©cepteurs membranaires ou encore lâinfection par des particules virales, dĂ©pendent toutes de lâentrĂ©e de molĂ©cules dans la cellule. Une fois lâendocytose dĂ©pendante de la clathrine bien caractĂ©risĂ©e, il est apparu que dâautres processus dâentrĂ©e, qui ne mettent pas en jeu la clathrine, existent Ă©galement dans la cellule. Cette synthĂšse a pour but de faire le point sur les avancĂ©es rĂ©centes qui Ă©tablissent avec certitude lâexistence des voies dâendocytose indĂ©pendantes de la clathrine, et qui mettent en Ă©vidence leurs rĂ©gulations spĂ©cifiques
Interferon gamma receptor: The beginning of the journey
Our view of endocytosis and membrane trafficking of transmembrane receptors has dramatically changed over the last 20 years. Several new endocytic routes have been discovered and mechanistically characterized in mammalian cells. Long considered as a passive means to terminate signaling through down-regulation of the number of activated receptors at the plasma membrane, it is now established that receptor endocytosis and endosomal sorting can be directly linked to the regulation of intracellular signaling pathways. The functional links between membrane trafficking of interferon receptors and JAK/STAT signaling have recently begun to be unraveled. These studies raise the exciting possibility that a certain level of signal specificity can be achieved through endocytosis and selective localization of the activated complexes within cellular membranes. The ongoing development of high-resolution cell imaging techniques with better spatial and temporal resolution gives new means of deciphering the inherent complexity of membrane trafficking and signaling. This should help to better comprehend the molecular mechanisms by which endocytosis and endosomal sorting of interferon receptors can orchestrate signaling selectivity within the JAK/STAT pathway that can be activated by as many as 60 different cytokines, growth factors, and hormones
Receptor lipid nanodomain partitioning and signaling
International audienceNo abstract availabl
Dynamiques molĂ©culaire et membranaire du rĂ©cepteur de lâinterfĂ©ron gammaâŻ: pour un sucre de tropâŻ!
International audienceNo abstract availabl
The lipoatrophic caveolin-1 deficient mouse model reveals autophagy in mature adipocytes
STAM and Hrs interact sequentially with IFN-α Receptor to control spatiotemporal JAKâSTAT endosomal activation
Activation of the JAK-STAT pathway by type I interferons (IFNs) requires clathrin-dependent endocytosis of the IFN-α and -ÎČ receptor (IFNAR), indicating a role for endosomal sorting in this process. The molecular machinery that brings the selective activation of IFN-α/ÎČ-induced JAK-STAT signalling on endosomes remains unknown. Here we show that the constitutive association of STAM with IFNAR1 and TYK2 kinase at the plasma membrane prevents TYK2 activation by type I IFNs. IFN-α-stimulated IFNAR endocytosis delivers the STAM-IFNAR complex to early endosomes where it interacts with Hrs, thereby relieving TYK2 inhibition by STAM and triggering signalling of IFNAR at the endosome. In contrast, when stimulated by IFN-ÎČ, IFNAR signalling occurs independently of Hrs as IFNAR is sorted to a distinct endosomal subdomain. Our results identify the molecular machinery that controls the spatiotemporal activation of IFNAR by IFN-α and establish the central role of endosomal sorting in the differential regulation of JAK-STAT signalling by IFN-α and IFN-ÎČ