A5073426409- Cellular transport and secretion
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Cardiomyopathy and Myosin Studies
- Force Microscopy Techniques and Applications
- Endoplasmic Reticulum Stress and Disease
- Chronic Lymphocytic Leukemia Research
- Protein Degradation and Inhibitors
- Cell Adhesion Molecules Research
- Lipid Membrane Structure and Behavior
- Autophagy in Disease and Therapy
- Microfluidic and Bio-sensing Technologies
- Lymphoma Diagnosis and Treatment
- Neurofibromatosis and Schwannoma Cases
- Photosynthetic Processes and Mechanisms
- Toxoplasma gondii Research Studies
- Biochemical and Molecular Research
- Metal Forming Simulation Techniques
- Muscle Physiology and Disorders
- RNA Interference and Gene Delivery
- Microbial Inactivation Methods
- Biochemical and Structural Characterization
Institut Curie
2016-2024
Nurix (United States)
2023-2024
Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes
2022-2024
Physique des Cellules et Cancers
2024
Centre National de la Recherche Scientifique
2016-2023
Université Paris Sciences et Lettres
2016-2023
Université de Toulouse
2021
Université Toulouse III - Paul Sabatier
2021
Institut de Pharmacologie et de Biologie Structurale
2021
Sorbonne Université
2018-2019
Increasing use of covalent and noncovalent inhibitors Bruton's tyrosine kinase (BTK) has elucidated a series acquired drug-resistant BTK mutations in patients with B cell malignancies. Here we identify inhibitor resistance distinct enzymatic activities, including some that impair activity while imparting novel protein-protein interactions sustain receptor (BCR) signaling. Furthermore, describe clinical-stage IKZF1/3 degrader, NX-2127, can bind proteasomally degrade each mutant proteoform,...
To ensure their homeostasis and sustain differentiated functions, cells continuously transport diverse cargos to various cell compartments in particular the surface. Secreted proteins are transported along intracellular routes from endoplasmic reticulum through Golgi complex before reaching plasma membrane microtubule tracks. Using a synchronized secretion assay, we report here that exocytosis does not occur randomly at surface but on localized hotspots juxtaposed focal adhesions. Although...
The actin and microtubule cytoskeletons play important roles in Golgi structure function, but how they are connected remain poorly known. In this study, we investigated whether RAB6 GTPase, a Golgi-associated RAB involved the regulation of several transport steps at level, two its effectors, Myosin IIA KIF20A participate coupling between cytoskeleton. We have previously shown that RAB6-Myosin interaction is critical for fission RAB6-positive carriers from Golgi/TGN membranes. Here show also...
One challenge in cell biology is to decipher the biophysical mechanisms governing protein enrichment on curved membranes and resulting membrane deformation. The ERM ezrin abundant associated with cellular that are flat, positively or negatively curved. Using vitro approaches, we assess of ezrin’s membranes. We evidence wild-type (ezrinWT) its phosphomimetic mutant T567D (ezrinTD) do not deform but self-assemble anti-parallelly, zipping adjacent EzrinTD’s specific conformation reduces...
Abstract Accurate sorting of proteins to the three types parasite-specific secretory organelles namely rhoptry, microneme and dense granule in Toxoplasma gondii is crucial for successful host cell invasion by this obligate intracellular parasite. Despite its tiny body architecture limited trafficking machinery, T. relies heavily on transport vesicles containing proteins, lipids important virulence-like factors that are delivered these organelles. However, our understanding how operates...
Specific intracellular localization of RAB GTPases has been reported to be dependent on protein factors, but the contribution membrane physicochemical properties this process poorly described. Here, we show that three proteins (RAB1/RAB5/RAB6) preferentially bind in vitro disordered and curved membranes, feature is uniquely their prenyl group. Our results imply addition a group confers proteins, most probably also other prenylated ability sense lipid packing defects induced by unsaturated...
Abstract The regulation of actin dynamics is essential for various cellular processes. Former evidence suggests a correlation between the function non-conventional myosin motors and dynamics. Here we investigate contribution 1b to using sliding motility assays. We observe that on immobilized or bound fluid bilayer enhances depolymerization at barbed end, while II, although 5 times faster, has no effect. This work reveals motor as another type depolymerase points its singular interactions with end.
Motile and morphological cellular processes require a spatially temporally coordinated branched actin network that is controlled by the activity of various regulatory proteins, including Arp2/3 complex, profilin, cofilin tropomyosin. We have previously reported myosin 1b regulates density in growth cone. Here, performing vitro F-actin gliding assays total internal reflection fluorescence (TIRF) microscopy, we show this molecular motor flattens (reduces branch angle) Arp2/3-dependent...
Abstract Amphiphysin 2 (BIN1) is a membrane and actin remodeling protein mutated in congenital adult centronuclear myopathies. Here, we report an unexpected function of this N-BAR domain BIN1 filopodia formation. We demonstrated that expression necessary sufficient to induce present at the base forming all along filopodia, where it colocalizes with F-actin. identify BIN1-mediated formation requires IRSp53, which allows its localization negatively-curved topologies. Our results show bundles...
Abstract The regulation of actin dynamics is essential for various cellular processes. Former evidence suggests a correlation between the function non-conventional myosin motors and dynamics. We investigate contribution myosin1b to using sliding motility assays. observe that on immobilized or bound fluid bilayer enhances depolymerization at barbed end, while II, although 5 times faster, has no effect. This work reveals motor as new type depolymerase points its singular interactions with end.
Abstract RAB GTPases are key regulators of membrane trafficking in eukaryotic cells. In addition to their role interphase, several proteins, including Golgi-associated RAB6, have mitotic functions. The aim this study was investigate how the interphasic and functions RAB6 could be regulated. Since phosphorylation is a regulatory process mitosis, we looked for specific using phospho-proteomic approach. We found that phosphorylated at position S52 by kinase Pololike 1 (Plk1) mitosis....
Abstract Small molecule kinase inhibitors have revolutionized the treatment of hematological malignancies by suppressing signaling pathways essential for tumor cell survival. Bruton’s Tyrosine Kinase (BTK) are widely used in clinic patients with B malignancies. Acquired resistance mutations, however, can reduce or eliminate their efficacy and represent a growing challenge. Mutations at C481 dramatically binding covalent BTK inhibitors, whereas other clinically-observed mutations such as...
Abstract Motile and morphological cellular processes require a spatially temporally coordinated branched actin network that is controlled by the activity of various regulatory proteins including Arp2/3 complex, profilin, cofilin tropomyosin. We have previously reported myosin 1b regulates density in growth cone. Using vitro F-actin gliding assays total internal reflection fluorescence (TIRF) microscopy we show this report molecular motor flattens Arp2/3-dependent branches up to breaking them...
Abstract One challenge in current cell biology is to decipher the biophysical mechanisms governing protein enrichment on curved membranes and resulting membrane deformation. The ERM ezrin abundant associated with cellular that are flat or positive negative curvatures. Using vitro approaches, we assess of ezrin’s membranes. We evidence (ezrinWT) its phosphomimetic mutant T567D (ezrinTD) do not deform but self-assemble anti-parallelly, zipping adjacent EzrinTD’s specific conformation reduces...
Abstract Amphiphysin 2 (BIN1) is a membrane and actin remodeling protein mutated in congenital adult centronuclear myopathies. Here, we report an unexpected function of this N-BAR domain BIN1 filopodia formation. We demonstrated that expression necessary sufficient to induce present at the base forming all along filopodia, where it colocalizes with F-actin. identify BIN1-mediated formation requires IRSp53, which allows its localization negatively-curved topologies. Our results show bundles...