STAM Interaction with Hrs Controls JAK/STAT Activation by Interferon-α at the Early Endosome

Zanin, Natacha; Blouin, Cédric M.; Cv, de Lesegno; Chmiest, Daniela; Johannes, Ludger; Lamaze, Christophe

doi:10.1101/509968

Cited by 5 publications

(7 citation statements)

References 45 publications

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“…Recording neuronal activity using optical methods has been a long-standing quest for neuroscientists as it promises a noninvasive means to probe real-time dynamic neuronal function. Imaging neuronal calcium transients (somatic calcium concentration changes) with genetically encoded calcium indicators (43,44), fluorescent calcium indicator stains (45), and two-photon excitation methods using galvanometric (46) and target-path scanners (47) have been used to resolve suprathreshold spiking (electrical) activity.…”

Section: Resultsmentioning

confidence: 99%

High-speed compressed-sensing fluorescence lifetime imaging microscopy of live cells

Lee

Best-Popescu

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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We present high-resolution, high-speed fluorescence lifetime imaging microscopy (FLIM) of live cells based on a compressed sensing scheme. By leveraging the compressibility of biological scenes in a specific domain, we simultaneously record the time-lapse fluorescence decay upon pulsed laser excitation within a large field of view. The resultant system, referred to as compressed FLIM, can acquire a widefield fluorescence lifetime image within a single camera exposure, eliminating the motion artifact and minimizing the photobleaching and phototoxicity. The imaging speed, limited only by the readout speed of the camera, is up to 100 Hz. We demonstrated the utility of compressed FLIM in imaging various transient dynamics at the microscopic scale.

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Section: Resultsmentioning

confidence: 99%

High-speed compressed-sensing fluorescence lifetime imaging microscopy of live cells

Lee

Best-Popescu

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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“…Nuclear translocation of STAT1 was quantified with a homemade plugin [52] by calculating the nucleo-cytoplasmic ratio of phospho-STAT1 signal. Nuclei masks were realized thanks to DAPI staining.…”

Section: Methodsmentioning

confidence: 99%

Plasma membrane nanodeformations promote actin polymerisation through CIP4/CDC42 recruitment and regulate type II IFN signaling

Ledoux

Zanin

Yang

et al. 2022

Preprint

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In their environment, cells have to cope with mechanical stresses constantly. Among those, nanoscale deformations of plasma membrane induced by substrate nanotopography are now largely accepted as a biophysical stimulus influencing cell behaviour and function. However, the mechanotransduction cascades involved and their precise molecular effects on cellular physiology are still poorly understood. Here, using homemade fluorescent nanostructured cell culture surfaces, we explored the role of Bin/Amphiphysin/Rvs (BAR) domain proteins as mechanosensors of plasma membrane geometry. Our data reveal that distinct subsets of BAR proteins bind to plasma membrane deformations in a membrane curvature radius-dependent manner. Furthermore, we show that membrane curvature promotes the formation of dynamic actin structures mediated by the Rho GTPase CDC42, the F-BAR protein CIP4 and the presence of PI(4,5)P2, independently of clathrin. In addition, these actin-enriched nanodomains can serve as platforms to regulate receptor signaling as they appear to contain Interferon γ receptor (IFNγ-R) and to lead to the partial inhibition of IFNγ-induced Janus-activated tyrosine kinase/signal transducer and activator of transcription (JAK/STAT) signaling.

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“…Indeed, the endosomal sorting machinery appears to play a critical role in defining JAK/STAT signalling by IFNs. Signal‐transducing adaptor molecule (STAM2), a member of the endosomal sorting complex required for transport complex (ESCRT‐0) [ 211 ], interacts with IFNAR1 and TYK2 in the plasma membrane, blocking the activation of the latter in resting conditions [ 212 ]. Upon IFNα2 stimulation, the IFN‐receptor complex translocates to early endosomes rich in PI(3)P, where hepatocyte growth factor‐regulated tyrosine kinase substrate (Hrs) binds to STAM2, blocking its inhibitory effects and promoting IFN endosomal signalling [ 212 ].…”

Section: Cytokine‐receptor Endosomal Traffic and Signallingmentioning

confidence: 99%

Molecular and cellular factors determining the functional pleiotropy of cytokines

2022

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Cytokines are soluble factors vital for mammalian physiology. Cytokines elicit highly pleiotropic activities, characterized by their ability to induce a wide spectrum of functional responses in a diverse range of cell subsets, which makes their study very challenging. Cytokines activate signalling via receptor dimerization/oligomerization, triggering activation of the JAK (Janus kinase)/STAT (signal transducer and activator of transcription) signalling pathway. Given the strong crosstalk and shared usage of key components of cytokine signalling pathways, a long-standing question in the field pertains to how functional diversity is achieved by cytokines. Here, we discuss how biophysicalfor example, ligand-receptor binding affinity and topologyand cellularfor example, receptor, JAK and STAT protein levels, endosomal compartmentparameters contribute to the modulation and diversification of cytokine responses. We review how these parameters ultimately converge into a common mechanism to fine-tune cytokine signalling that involves the control of the number of Tyr residues phosphorylated in the receptor intracellular domain upon cytokine stimulation. This results in different kinetics of STAT activation, and induction of specific gene expression programs, ensuring the generation of functional diversity by cytokines using a limited set of signalling intermediaries. We describe how these first principles of cytokine signalling have been exploited using protein engineering to design cytokine variants with more specific and less toxic responses for immunotherapy.

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STAM Interaction with Hrs Controls JAK/STAT Activation by Interferon-α at the Early Endosome

Cited by 5 publications

References 45 publications

High-speed compressed-sensing fluorescence lifetime imaging microscopy of live cells

High-speed compressed-sensing fluorescence lifetime imaging microscopy of live cells

Plasma membrane nanodeformations promote actin polymerisation through CIP4/CDC42 recruitment and regulate type II IFN signaling

Molecular and cellular factors determining the functional pleiotropy of cytokines

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