A5043981713- Microtubule and mitosis dynamics
- Neuroscience and Neuropharmacology Research
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Genetic and Kidney Cyst Diseases
- Pluripotent Stem Cells Research
- Receptor Mechanisms and Signaling
- Nuclear Receptors and Signaling
- Adenosine and Purinergic Signaling
- Photosynthetic Processes and Mechanisms
- Signaling Pathways in Disease
- Alzheimer's disease research and treatments
- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
- Caveolin-1 and cellular processes
- Gastrointestinal motility and disorders
- Cellular transport and secretion
- 14-3-3 protein interactions
- Hippo pathway signaling and YAP/TAZ
- Neuroscience of respiration and sleep
- Genomics and Chromatin Dynamics
- Autism Spectrum Disorder Research
- Lipid Membrane Structure and Behavior
- Neuroblastoma Research and Treatments
- Nitric Oxide and Endothelin Effects
University of Lisbon
2023-2025
Institute for Research in Biomedicine
2016-2024
Institute of Science and Technology
2021
Universidade do Porto
2015
Neurons display a highly polarized microtubule network that mediates trafficking throughout the extensive cytoplasm and is crucial for neuronal differentiation function. In newborn migrating neurons, organized by centrosome. During neuron maturation, however, centrosome gradually loses this activity, how microtubules are in more mature neurons remains poorly understood. Here, we demonstrate organization post-mitotic strongly depends on non-centrosomal nucleation mediated augmin nucleator...
During development, neurons achieve a stereotyped neuron type-specific morphology, which relies on dynamic support by microtubules (MTs). An important player is the augmin complex (hereafter augmin), binds to existing MT filaments and recruits γ-tubulin ring (γ-TuRC), form branched MTs. In cultured neurons, for neurite formation. However, little known about role of during formation in vivo. Here, we have revisited mammalian culture then turned towards class four Drosophila dendritic...
Abstract Centriole biogenesis and maintenance are crucial for cells to generate cilia assemble centrosomes that function as microtubule organizing centers (MTOCs). MTOC both require the nucleator γ-tubulin ring complex (γTuRC). It is widely accepted γTuRC nucleates microtubules from pericentriolar material associated with proximal part of centrioles. However, also localizes more distally in centriole lumen, but significance these findings unclear. Here we identify spatially functionally...
In Alzheimer's disease (AD), amyloid β (Aβ)-triggered cleavage of TrkB-FL impairs brain-derived neurotrophic factor (BDNF) signaling, thereby compromising neuronal survival, differentiation, and synaptic transmission plasticity. Using cerebrospinal fluid postmortem human brain samples, we show that occurs from the early stages increases as a function pathology severity. To explore therapeutic potential this mechanism, designed small TAT-fused peptides screened their ability to prevent...
Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival, differentiation, and plasticity. In epilepsy, BDNF exhibits a dual role, exerting both antiepileptic pro-epileptic effects. The cleavage of its main receptor, full-length tropomyosin-related kinase B (TrkB-FL), was suggested to occur in status epilepticus (SE) vitro. Moreover, under excitotoxic conditions, TrkB-FL found be cleaved, resulting the formation new intracellular fragment, TrkB-ICD. Thus, we hypothesized...
Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival, differentiation, and plasticity. In epilepsy, BDNF exhibits a dual role, exerting both antiepileptic pro-epileptic effects. The cleavage of its main receptor, full-length tropomyosin-related kinase B (TrkB-FL), was suggested to occur in status epilepticus (SE) vitro. Moreover, under excitotoxic conditions, TrkB-FL found be cleaved, resulting the formation new intracellular fragment, TrkB-ICD. Thus, we hypothesized...
Abstract Neural cell adhesion molecule 2 (NCAM2) is involved in the development and plasticity of olfactory system. Genetic data have implicated NCAM2 gene neurodevelopmental disorders including Down syndrome autism, although its role cortical unknown. Here, we show that while overexpression hippocampal neurons leads to minor alterations, downregulation severely compromises dendritic architecture, leading an aberrant phenotype shorter trees, retraction dendrites, emergence numerous somatic...
Gastrointestinal smooth muscle relaxation is accomplished by the neural corelease of ATP or a related purine and nitric oxide. Contractions are triggered acetylcholine tachykinins. The aim this work was to study whether regional differences in neurotransmission could partially explain varied physiological roles each colonic area.We used electrophysiological myography techniques evaluate purinergic (L-NNA 1 mm incubated tissue), nitrergic (MRS2500 0.3 μm tissue) cholinergic MRS2500 proximal,...
Microtubules that assemble the mitotic spindle are generated by centrosomal nucleation, chromatin-mediated and nucleation from surface of other microtubules mediated augmin complex. Impairment in apical progenitors developing mouse brain induces p53-dependent apoptosis causes non-lethal microcephaly. Whether disruption non-centrosomal has similar effects is unclear. Here, we show, using embryos, conditional knockout subunit Haus6 led to defects delay. This triggered massive abortion...
The primary cilium, a microtubule-based sensory organelle, undergoes cycles of assembly and disassembly that govern the cell cycle progression critical to proliferation differentiation. Although cilia has been studied extensively, molecular mechanisms underlying are less well understood. Here, we uncover γ-tubulin ring complex (γ-TuRC)-dependent pathway promotes thereby prevents formation. We further demonstrate Kif2A, kinesin motor bears microtubule-depolymerizing activity, is recruited...
Rett Syndrome is an X-linked neurodevelopmental disorder (RTT; OMIM#312750) associated to MECP2 mutations. MeCP2 dysfunction seen as one cause for the deficiencies found in brain-derived neurotrophic factor (BDNF) signaling, since BDNF of genes under jurisdiction. signaling also dependent on proper function adenosinergic system. Indeed, both and system are altered Mecp2-null mice (Mecp2−/y), a representative model severe manifestation RTT. Considering that symptoms severity largely differs...
Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival, differentiation, and plasticity. In epilepsy, BDNF exhibits a dual role, exerting both antiepileptic pro-epileptic effects. The cleavage of its main receptor, full-length tropomyosin-related kinase B (TrkB-FL), was suggested to occur in status epilepticus (SE) vitro. Moreover, under excitotoxic conditions, TrkB-FL found be cleaved, resulting the formation new intracellular fragment, TrkB-ICD. Thus, we hypothesized...
Abstract Centriole biogenesis and maintenance are crucial for cells to generate cilia assemble centrosomes that function as microtubule organizing centers (MTOCs). MTOC both require the nucleator γ-tubulin ring complex (γTuRC). The widely accepted view is γTuRC localizes pericentriolar material (PCM), where it nucleates microtubules. has also been observed at centriolar regions lack PCM, but significance of these findings unclear. Here we have used expansion microscopy map spatially...
Summary Microtubules that assemble the mitotic spindle are generated by three different mechanisms: centrosomal nucleation, chromatin-mediated and nucleation from surface of other microtubules mediated augmin complex. Impairment in apical progenitors developing mouse brain induces p53-dependent apoptosis causes non-lethal microcephaly. Whether disruption non-centrosomal has similar effects is unclear. Here we show, using embryos, conditional knockout subunit Haus6 led to defects delay. This...