A5035043270- Nuclear Structure and Function
- Cellular Mechanics and Interactions
- Muscle Physiology and Disorders
- RNA Research and Splicing
- Microtubule and mitosis dynamics
- Cardiomyopathy and Myosin Studies
- Cellular transport and secretion
- Neurogenetic and Muscular Disorders Research
- Photodynamic Therapy Research Studies
- Single-cell and spatial transcriptomics
- Cell Adhesion Molecules Research
- Mitochondrial Function and Pathology
- Neuroscience and Neural Engineering
- Tissue Engineering and Regenerative Medicine
- Genomics and Chromatin Dynamics
- 3D Printing in Biomedical Research
- Signaling Pathways in Disease
- Neurobiology and Insect Physiology Research
- RNA Interference and Gene Delivery
- Cancer, Hypoxia, and Metabolism
- Nitric Oxide and Endothelin Effects
- Porphyrin and Phthalocyanine Chemistry
- Hereditary Neurological Disorders
- Wnt/β-catenin signaling in development and cancer
- Electrospun Nanofibers in Biomedical Applications
Institute for Molecular Medicine
2025
University of Lisbon
2015-2024
Instituto Politécnico de Lisboa
2023
Instituto de Medicina Molecular João Lobo Antunes
2015-2022
Sorbonne Université
2010-2021
Centre de Recherche en Myologie
2015-2021
Centre National de la Recherche Scientifique
2016-2021
Inserm
2010-2021
University of Coimbra
2002-2020
Institute of Molecular Medicine
2018-2019
Nuclei move to specific locations polarize migrating and differentiating cells. Many nuclear movements are microtubule-dependent. However, movement reorient the centrosome in fibroblasts occurs through an unknown actin-dependent mechanism. We found that linear arrays of outer (nesprin2G) inner (SUN2) membrane proteins assembled on moved with retrogradely moving dorsal actin cables during polarizing fibroblasts. Inhibition nesprin2G, SUN2, or prevented reorientation. The coupling for via...
Mutations in the AAA adenosine triphosphatase (ATPase) Spastin (SPG4) cause an autosomal dominant form of hereditary spastic paraplegia, which is a retrograde axonopathy primarily characterized pathologically by degeneration long spinal neurons corticospinal tracts and dorsal columns. Using recombinant Spastin, we find that six mutant forms including three disease-associated forms, are severely impaired ATPase activity. In contrast to mutation designed prevent triphosphate (ATP) binding, ATP...
The linker of nucleoskeleton and cytoskeleton (LINC) complex is situated in the nuclear envelope forms a connection between lamina cytoskeletal elements. Sun1, Sun2 nesprin-2 are important components LINC complex. We expressed these proteins fused to green fluorescent protein embryonic fibroblasts studied their diffusional mobilities using fluorescence recovery after photobleaching. show that they all more mobile from mice lacking A-type lamins than cells wild-type mice. Knockdown also...
The nucleus is the main microtubule-organizing center (MTOC) in muscle cells due to accumulation of centrosomal proteins and microtubule (MT) nucleation activity at nuclear envelope (NE) [1Bugnard E. Zaal K.J.M. Ralston Reorganization during differentiation.Cell Motil. Cytoskeleton. 2005; 60: 1-13Crossref PubMed Scopus (113) Google Scholar, 2Fant X. Srsen V. Espigat-Georger A. Merdes Nuclei non-muscle bind centrosome upon fusion with differentiating myoblasts.PLoS ONE. 2009; 4: e8303Crossref...
Nuclear position is actively controlled and can be adjusted according to the needs of a cell by nuclear movement. Microtubules mediate majority movements studied date, although examples mediated actin cytoskeleton have been described. One such actin-dependent movement occurs during centrosome orientation in fibroblasts polarizing for migration. Here, maintained at center while nucleus moved rear retrograde flow thus positioning between leading edge cell. We explored molecular mechanism...
Cancer cells' ability to migrate through constricting pores in the tissue matrix is limited by nuclear stiffness. MT1-MMP contributes metastasis widening pores, facilitating confined migration. Here, we show that modulation of pore size or lamin A expression known modulate stiffness directly impinges on levels MT1-MMP-mediated pericellular collagenolysis cancer cells. component this adaptive response centrosome-centered distribution intracellular storage compartments ahead nucleus. We...
Abstract Mutations in amphiphysin‐2/ BIN 1, dynamin 2, and myotubularin are associated with centronuclear myopathy ( CNM ), a muscle disorder characterized by myofibers atypical central nuclear positioning abnormal triads. Mis‐splicing of 1 is also myotonic dystrophy that shares histopathological hallmarks . How amphiphysin‐2 orchestrates triad organization how ‐associated mutations lead to dysfunction remains elusive. We find N‐ WASP interacts this interaction distribution disrupted...
Muscle repair without stem cells Skeletal muscle is a mechanical organ that endures cellular damage after contraction. Lesions caused by external injury can be repaired cells, which fuse with injured or create entirely new myofibers. Roman et al . describe cell-autonomous process independent of (see the Perspective McNally and Demonbreun). After localized damage, myonuclei migrate to sites locally deliver messenger RNA for reconstruction. This myofiber self-repair represents model...
Cytoplasmic dynein has been implicated in numerous aspects of intracellular movement. We recently found inhibitors to interfere with the reorientation microtubule cytoskeleton during healing wounded NIH3T3 cell monolayers. now find that and its regulators dynactin LIS1 localize leading cortex this process. In presence serum, bright diffuse staining was observed regions active ruffling. This pattern abolished by cytochalasin D, not cells treated lysophosphatidic acid, conditions which allow...
The position of the nucleus is regulated in different developmental stages and cellular events. During polarization, moves away from future leading edge this movement required for proper cell migration. Nuclear requires LINC complex components nesprin-2G SUN2, which form transmembrane actin-associated nuclear (TAN) lines at envelope. Here we show that envelope protein Samp1 (NET5) involved during fibroblast polarization Moreover, demonstrate a component TAN contain SUN2. Finally, associates...
LINC complexes are transmembrane protein assemblies that physically connect the nucleoskeleton and cytoskeleton through nuclear envelope. Dysfunctions of associated with pathologies such as cancer muscular disorders. The mechanical roles poorly understood. To address this, we used genetically encoded FRET biosensors molecular tension in a nesprin complex fibroblastic epithelial cells culture. We exposed to mechanical, genetic, pharmacological perturbations, mimicking range physiological...
Skeletal muscle myofibers are large and elongated cells with multiple evenly distributed nuclei. Nuclear distribution suggests that each nucleus influences a specific compartment within the myofiber implies functional role for nuclear positioning. Compartmentalization of mRNAs proteins has been reported at neuromuscular myotendinous junctions, but mRNA in non-specialized regions remains largely unexplored. We report bulk enriched around origin this perinuclear accumulation depends on...
Nuclear positioning is a determining event in several cellular processes, such as fertilization, cell migration, and differentiation. The structure function of muscle cells, which contain hundreds nuclei, have been shown to rely part on proper nuclear positioning. Remarkably, the course differentiation, movements along myotube axis might represent required for even nuclei mature myofiber. Here we analyze behavior, time motion, speed, alignment during differentiation temporal interference...