A5043615577- Microtubule and mitosis dynamics
- Genetic and Kidney Cyst Diseases
- Photosynthetic Processes and Mechanisms
- Chromosomal and Genetic Variations
- Ubiquitin and proteasome pathways
- Cellular transport and secretion
- Epigenetics and DNA Methylation
- 14-3-3 protein interactions
- Fibroblast Growth Factor Research
- Muscle Physiology and Disorders
- Protist diversity and phylogeny
- Reproductive Biology and Fertility
- Mechanisms of cancer metastasis
- Plant Reproductive Biology
- Amino Acid Enzymes and Metabolism
- ATP Synthase and ATPases Research
- Cellular Mechanics and Interactions
- Nuclear Structure and Function
- Protein Structure and Dynamics
- Pluripotent Stem Cells Research
University of Cambridge
2010-2020
University of Edinburgh
2005-2015
Wellcome Centre for Cell Biology
2005-2015
Cancer Research UK
2012
Centrioles are 9-fold symmetrical structures at the core of centrosomes and base cilia whose dysfunction has been linked to a wide range inherited diseases cancer [1Nigg E.A. Raff J.W. Centrioles, centrosomes, in health disease.Cell. 2009; 139: 663-678Abstract Full Text PDF PubMed Scopus (683) Google Scholar]. Their duplication is regulated by protein kinase conserved structure, C. elegans ZYG-1 or its Polo-like 4 (Plk4) counterpart other organisms [2O'Connell K.F. Caron Kopish K.R. Hurd...
Microtubule-based transport mediates the sorting and dispersal of many cellular components pathogens. However, mechanisms by which motor complexes are recruited to regulated on different cargos remain poorly understood. Here we describe a large-scale biochemical screen for novel factors associated with RNA localization signals mediating minus end–directed mRNA during Drosophila development. We identified protein Lissencephaly-1 (Lis1) found that minus-end travel distances localizing...
The conserved process of centriole duplication requires Plk4 kinase to recruit and promote interactions between Sas6 Sas5/Ana2/STIL (respective nomenclature worms/flies/humans). Plk4-mediated phosphorylation Ana2/STIL in its STAN motif has been shown interaction with Sas6. However, is not required for recruitment Ana2 the centriole. Here we show that Drosophila, loads onto site procentriole formation ahead a also Plk4. whereas first recruited multiple sites around ring zone II at periphery...
Axons act like cables, electrically wiring the nervous system. Polar bundles of microtubules (MTs) form their backbones and drive growth. Plus end–tracking proteins (+TIPs) regulate MT growth dynamics directionality at plus ends. However, current knowledge about +TIP functions, mostly derived from work in vitro nonneuronal cells, may not necessarily apply to very different context axonal MTs. For example, CLIP family +TIPs are known polymerization promoters cells. we show here that neither...
Mutations in Drosophila merry-go-round (mgr) have been known for over two decades to lead circular mitotic figures and loss of meiotic spindle integrity. However, the identity its gene product has remained undiscovered. We now show that mgr encodes Prefoldin subunit counterpart human von Hippel Lindau binding-protein 1. Depletion Mgr from cultured cells also leads formation monopolar abnormal spindles centrosome loss. These phenotypes are associated with reductions tubulin levels both flies...
CLIP-170 was the first microtubule plus-end-tracking protein to be described, and is implicated in regulation of plus-ends their interaction with other cellular structures. Here, we have studied cell-cycle-dependent mechanisms which localise sole Drosophila melanogaster homologue CLIP-190. During mitosis, CLIP-190 localises unattached kinetochores independently spindle-checkpoint activation. This localisation depends on dynein-dynactin complex Lis1 also kinetochores. Further analysis...
Little is known about how microtubules are regulated in different cell types during development. EB1 plays a central role the regulation of microtubule plus ends. It directly binds to ends and recruits proteins which regulate dynamics behaviour. We report identification Kank, sole Drosophila orthologue human Kank proteins, as an interactor that predominantly localises embryonic attachment sites between muscle tendon cells. Human Kank1 was identified tumour suppressor has documented roles...
Rcd4 is a poorly characterized Drosophila centriole component whose mammalian counterpart, PPP1R35, suggested to function in elongation and conversion centrosomes. Here, we show that rcd4 mutants exhibit fewer centrioles, aberrant mitoses, reduced basal bodies sensory organs. interacts with the C-terminal part of Ana3, which loads onto procentriole during interphase, ahead before mitosis. Accordingly, depletion Ana3 prevents recruitment but not vice versa. We find neither nor participates...
Microtubule plus ends are dynamic that interact with other cellular structures. end tracking proteins considered to play important roles in the regulation of microtubule ends. Recent studies revealed EB1 is central regulator for by recruiting them through direct interaction. Here we report identification a novel Drosophila protein, which call Kebab (kinetochore and associated basic protein), vitro expression screening EB1-interacting proteins. fused GFP shows pattern localisation mitosis. It...
The centriole is a ninefold symmetrical structure found at the core of centrosomes and, as basal body, base cilia, whose conserved duplication regulated by Plk4 kinase. phosphorylates single serine residue N-terminus Ana2 to promote Ana2's loading site procentriole formation. Four serines in STAN motif are then phosphorylated Plk4, enabling Sas6 recruitment. Crystallographic data indicate that coiled–coil domain forms tetramer but full-length has not been solved. Here, we have employed...
Abstract Genome wide screens are widely believed to have identified the great majority of genes required for centriole duplication. However, seeking clarify partners Drosophila cartwheel protein Sas6, we Gorab, a known trans-Golgi associated that is mutated in human wrinkly skin disease, gerodermia osteodysplastica. We now report Gorab present not only but also association with Sas6 at core centriole. Flies lacking show defects duplication many tissues and uncoordinated due basal body...