A5032878421- Microtubule and mitosis dynamics
- Genetics, Aging, and Longevity in Model Organisms
- Photosynthetic Processes and Mechanisms
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Protist diversity and phylogeny
- Cellular transport and secretion
- Cellular Mechanics and Interactions
- Geological Modeling and Analysis
- RNA Research and Splicing
- Cancer-related Molecular Pathways
- Genetic and Kidney Cyst Diseases
- Nuclear Structure and Function
- Ubiquitin and proteasome pathways
- Glycosylation and Glycoproteins Research
- Mitochondrial Function and Pathology
- DNA Repair Mechanisms
- Plant nutrient uptake and metabolism
- Cardiomyopathy and Myosin Studies
- Biocrusts and Microbial Ecology
- Insect Utilization and Effects
- RNA Interference and Gene Delivery
- Plant Molecular Biology Research
- Cancer-related molecular mechanisms research
- Advanced Electron Microscopy Techniques and Applications
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto
2015-2024
Universidade do Porto
2013-2024
Instituto de Biologia Molecular e Celular
2016-2023
University of California, San Diego
2010-2013
Ludwig Cancer Research
2006-2013
Ludwig Cancer Research
2008-2011
University of Edinburgh
2003-2008
Wellcome Centre for Cell Biology
2003-2008
University of Zurich
1959
From Genome to Regulatory Networks For biologists, having a genome in hand is only the beginning—much more investigation still needed characterize how used help produce functional organism (see Perspective by Blaxter ). In this vein, Gerstein et al. (p. 1775 ) summarize for Caenorhabditis elegans genome, and The modENCODE Consortium 1787 Drosophila melanogaster full transcriptome analyses over developmental stages, genome-wide identification of transcription factor binding sites,...
The chromosomal passenger complex of Aurora B kinase, INCENP, and Survivin has essential regulatory roles at centromeres the central spindle in mitosis. Here, we describe Borealin, a novel member complex. Approximately half mitotic cells is complexed with Survivin; Borealin binds INCENP vitro. A second contains but no or Survivin. Depletion by RNA interference delays progression results kinetochore–spindle misattachments an increase bipolar spindles associated ectopic asters. extra poles,...
Cytoplasmic dynein is a microtubule motor vital for cellular organization and division. It functions as ~4-megadalton complex containing its cofactor dynactin cargo-specific coiled-coil adaptor. However, how recognize diverse adaptors, they interact with each other during formation, the role of critical regulators such lissencephaly-1 (LIS1) protein remain unclear. In this study, we determined cryo–electron microscopy structure dynein-dynactin on microtubules LIS1 lysosomal adaptor JIP3....
We have used a human artificial chromosome (HAC) to manipulate the epigenetic state of chromatin within an active kinetochore. The HAC has dimeric alpha-satellite repeat containing one natural monomer with CENP-B binding site, and completely synthetic box replaced by tetracycline operator (tetO). This exhibits normal kinetochore protein composition mitotic stability. Targeting several tet-repressor (tetR) fusions into centromere had no effect on function. However, altering more open...
The spindle checkpoint generates a “wait anaphase” signal at unattached kinetochores to prevent premature anaphase onset. Kinetochore-localized dynein is thought silence the by transporting proteins from microtubule-attached poles. Throughout metazoans, recruitment requires protein Spindly. Here, we identify conserved motif in Spindly that essential for kinetochore targeting of dynein. mutants, expressed following depletion endogenous Spindly, target normally but recruitment. and despite...
Chromosome segregation requires stable bipolar attachments of spindle microtubules to kinetochores. The dynein/dynactin motor complex localizes transiently kinetochores and is implicated in chromosome segregation, but its role remains poorly understood. Here, we use the Caenorhabditis elegans embryo investigate function kinetochore dynein by analyzing Rod/Zwilch/Zw10 (RZZ) associated coiled-coil protein SPDL-1. Both components are essential for Mad2 targeting checkpoint activation. RZZ...
The molecular motor dynein concentrates at the kinetochore region of mitotic chromosomes in animals to accelerate spindle microtubule capture and control checkpoint signaling. In this study, we describe mechanism used by Rod–Zw10–Zwilch complex adaptor Spindly recruit kinetochores Caenorhabditis elegans embryos human cells. We show that Rod’s N-terminal β-propeller associated Zwilch subunit bind Spindly’s C-terminal domain, identify a specific mutant abrogates recruitment vivo binding Rod...
Dissecting Chromosome Segregation During cell division, the centromere regions of chromosomes assemble multiprotein organelles called kinetochores that form attachments to spindle microtubules. Working in Caenorhabditis elegans , Cheerambathur et al. (p. 1239 published online 14 November) describe a mechanism controlling formation kinetochore-spindle microtubule is essential for accurate chromosome segregation. The findings suggest existence crosstalk between two major protein complexes...
The MAP kinase and motor scaffold JIP3 prevents excess lysosome accumulation in axons of vertebrates invertebrates. How JIP3's interaction with dynein kinesin-1 contributes to organelle clearance is unclear. We show that human light intermediate chain (DLIC) binds the N-terminal RH1 domain JIP3, its paralog JIP4, lysosomal adaptor RILP. A point mutation abrogates DLIC binding without perturbing between kinesin heavy chain. Characterization this separation-of-function Caenorhabditis elegans...
Survivin is a key cellular protein thought to function in apoptotic regulation, mitotic progression, or possibly both. In this study, we describe the isolation of two conditional knockouts survivin gene chicken DT40 cells. cells lacking die interphase after failing complete cytokinesis. However, these show normal sensitivity chemotherapeutic agent etoposide. Expression mutants against null background reassess role several residues reveals that can grow normally if their sole missing widely...
Chromosome segregation requires coordinated separation of sister chromatids following biorientation all chromosomes on the mitotic spindle. Chromatid at metaphase-to-anaphase transition is accomplished by cleavage cohesin complex that holds together. Here we show using live-cell imaging extending metaphase bioriented state five independent perturbations (expression non-degradable Cyclin B, expression a Spindly point mutant prevents spindle checkpoint silencing, depletion anaphase inducer...
Spindle assembly checkpoint proteins have been thought to reside in the peripheral corona region of kinetochore, distal microtubule attachment sites at outer plate. However, recent biochemical evidence indicates that are closely linked core kinetochore site comprised Knl1–Mis12–Ndc80 (KMN) complexes/KMN network. In this paper, we show Knl1–Zwint1 complex is required recruit Rod–Zwilch–Zw10 (RZZ) and Mad1–Mad2 complexes kinetochore. Consistent with this, nanometer-scale mapping RZZ,...
All animal cells use the motor cytoplasmic dynein 1 (dynein) to transport diverse cargo toward microtubule minus ends and organize position arrays such as mitotic spindle. Cargo-specific adaptors engage with recruit activate motor, but molecular mechanisms remain incompletely understood. Here, we structural dynamic nuclear magnetic resonance (NMR) analysis demonstrate that C-terminal region of human light intermediate chain (LIC1) is intrinsically disordered contains two short conserved...
The clinical interest in farnesyltransferase inhibitors (FTIs) makes it important to understand how these compounds affect cellular processes involving farnesylated proteins. Mitotic abnormalities observed after treatment with FTIs have so far been attributed defects the farnesylation of outer kinetochore proteins CENP-E and CENP-F, which are involved chromosome congression spindle assembly checkpoint signaling. Here we identify cytoplasmic dynein adaptor Spindly as an additional component...
Cytokinesis completes cell division by constriction of an actomyosin contractile ring that separates the two daughter cells. Here we use early Caenorhabditis elegans embryo to explore how actin filament network in and surrounding cortex is regulated single cytokinesis formin CYK-1 ARP2/3 complex, which nucleate nonbranched branched filaments, respectively. We show complex are predominant F-actin nucleators responsible for generating distinct cortical architectures depletion either nucleator...
The microtubule-based motor dynein generates pulling forces for centrosome centration and mitotic spindle positioning in animal cells. How the essential activator dynactin regulates these functions of is incompletely understood. Here, we dissect role dynactin's microtubule binding activity, located p150 CAP-Gly domain an adjacent basic patch, C. elegans zygote. Analysis mutants engineered by genome editing suggests that tip tracking dynein-dynactin dispensable targeting to cell cortex...
Cytokinesis in animal cells requires the assembly and constriction of a contractile actomyosin ring. Non-muscle myosin II is essential for cytokinesis, but role its motor activity remains unclear. Here, we examine cytokinesis C. elegans embryos expressing non-muscle mutants generated by genome editing. Two motor-dead myosins capable binding F-actin do not support one-cell embryo, two partially motor-impaired delay render rings more sensitive to reduced levels. Further analysis suggests that...