A5044103344- Blood groups and transfusion
- Antioxidant Activity and Oxidative Stress
- Plant biochemistry and biosynthesis
- RNA modifications and cancer
- Photosynthetic Processes and Mechanisms
- Erythrocyte Function and Pathophysiology
- Genetic Neurodegenerative Diseases
- Cellular transport and secretion
- Genetics and Neurodevelopmental Disorders
- Reading and Literacy Development
- Endoplasmic Reticulum Stress and Disease
- Diabetes and associated disorders
- Algal biology and biofuel production
- RNA regulation and disease
- Mitochondrial Function and Pathology
- Neurological diseases and metabolism
- Cognitive and developmental aspects of mathematical skills
- Neurogenesis and neuroplasticity mechanisms
- Pancreatic function and diabetes
- Lipid Membrane Structure and Behavior
- Neuroscience and Music Perception
- Connective tissue disorders research
- Signaling Pathways in Disease
- Lysosomal Storage Disorders Research
- Glycosylation and Glycoproteins Research
Centre for Human Genetics
2012-2023
University of Oxford
2012-2023
Science Oxford
2008-2012
Universidad de Salamanca
1995-2011
St Vincent's Hospital Sydney
2008
New York Proton Center
2008
The VPS13A gene is associated with the neurodegenerative disorder Chorea Acanthocytosis. It unknown what consequences are of impaired function at subcellular level. We demonstrate that a peripheral membrane protein, mitochondria, endoplasmic reticulum and lipid droplets. localized sites where mitochondria in close contact. interacts ER residing protein VAP-A via its FFAT domain. Interaction mediated C-terminal In VPS13A-depleted cells, ER-mitochondria contact decreased, fragmented mitophagy...
The VPS13 gene family consists of VPS13A–D in mammals. Although all four genes have been linked to human diseases, their cellular functions are poorly understood, particularly those VPS13D. We generated and characterized knockouts each HeLa cells. Among the individual knockouts, only VPS13D-KO cells exhibit abnormal mitochondrial morphology. Additionally, VPS13D loss leads either partial or complete peroxisome several transformed cell lines fibroblasts derived from a mutation–carrying...
Abstract Chorea‐acanthocytosis (ChAc) is a severe, neurodegenerative disorder that shares clinical features with Huntington's disease and McLeod syndrome. It caused by mutations in VPS13A , which encodes large protein called chorein. Using antichorein antisera, we found expression of chorein all human cells analyzed. However, was absent or noticeably reduced ChAc patient cells, but not syndrome cells. This suggests loss diagnostic feature ChAc. Ann Neurol 2004;56:299–302
Using functional analyses in Escherichia coli and Mucor circinelloides , it has been shown that a single M. gene ( carRP ) codes for protein with two different enzymatic activities, lycopene cyclase phytoene synthase, which are encoded by independent genes organisms other than fungi. This was identified using complementation tests among classes of carotenoid mutants . The product contains domains: the R domain is located at N‐terminus determines activity; P C‐terminus displays synthase...
The transporter ATP7A mediates systemic copper absorption and provides cuproenzymes in the trans-Golgi network (TGN) with copper. To regulate metal homeostasis, constitutively cycles between TGN plasma membrane (PM). trafficking to PM is elevated response increased load reversed when concentrations are lowered. Molecular mechanisms underlying this poorly understood. We assess role of clathrin, adaptor complexes, lipid rafts, Rab22a an attempt decipher regulatory proteins involved cycling....
The KIAA0319 gene has been recently associated with developmental dyslexia and shown to be involved in neuronal migration. deduced protein contains several polycystic kidney disease (PKD) domains which may mediate the interaction between neurons glial fibres during We have previously reported presence of alternative splicing variants, some are predicted affect protein. In this study, we over-expressed constructs containing main form (A) two variants (B C) KIAA0319. show that full-length is a...
Galectin-12, a member of the galectin family β-galactoside-binding animal lectins, is preferentially expressed in adipocytes and required for adipocyte differentiation vitro. This protein was recently found to regulate lipolysis, whole body adiposity, glucose homeostasis vivo. Here we identify VPS13C, VPS13 vacuolar sorting-associated proteins highly conserved throughout eukaryotic evolution, as major galectin-12-binding protein. VPS13C upregulated during differentiation, galectin-12...
Chorea-Acanthocytosis is a rare, neurodegenerative disorder characterized by progressive loss of locomotor and cognitive function. It caused function mutations in the Vacuolar Protein Sorting 13A (VPS13A) gene, which conserved from yeast to human. The consequences VPS13A dysfunction nervous system are still largely unspecified. In order study protein ageing central we Drosophila melanogaster Vps13 mutant line. gene encoded similar size as human VPS13A. Our data suggest that peripheral...
KIAA0319 is a transmembrane protein associated with dyslexia presumed role in neuronal migration. Here we show that expression not restricted to the brain but also occurs sensory and spinal cord neurons, increasing from early postnatal stages adulthood being downregulated by injury. This suggested participates functions unrelated Supporting this hypothesis, overexpression of repressed axon growth hippocampal dorsal root ganglia neurons; intracellular domain was sufficient elicit effect. A...
Recently, genetic studies have implicated KIAA0319 in developmental dyslexia, the most common of childhood learning disorders. The first functional data indicated that protein is expressed on plasma membrane and may be involved neuronal migration. Further analysis subcellular distribution overexpressed mammalian cells indicates can colocalize with early endosomal marker endosome antigen 1 (EEA1) large intracellular vesicles, suggesting it endocytosed. Antibody internalization assays...
The KIAA0319 gene has been associated with reading disability in several studies. It encodes a plasma membrane protein large, highly glycosylated, extracellular domain. This is proposed to function adhesion and attachment thought play an important role during neuronal migration the developing brain. We have previously that endocytosis of this could constitute mechanism regulate its function. Here we show undergoes ectodomain shedding intramembrane cleavage. At least five different cleavage...
Phycomyces carRA gene encodes a protein with two domains. Domain R is characterized by red carR mutants that accumulate lycopene. A white carA do not significant amounts of carotenoids. The carRA-encoded was identified as the lycopene cyclase and phytoene synthase enzyme sequence homology other proteins. However, no direct data showing function this have been reported so far. Different Mucor circinelloides altered at synthase, or both activities were transformed gene. Fully transcribed mRNA...
Single nucleotide polymorphisms (SNPs) close to the VPS13C, C2CD4A and C2CD4B genes on chromosome 15q are associated with impaired fasting glucose increased risk of type 2 diabetes. eQTL analysis revealed an association between possession (C) alleles at a previously implicated causal SNP, rs7163757, lowered VPS13C levels in islets from female (n = 40, P < 0.041) but not male subjects. Explored using promoter-reporter assays β-cells other cell lines, variant rs7163757 enhancer activity. Mice...
Developmental dyslexia is a common disorder with strong genetic component, but the underlying molecular mechanisms are still unknown. Several candidate dyslexia-susceptibility genes, including KIAA0319, DYX1C1, and DCDC2, have been identified in humans. RNA interference experiments targeting these genes rat embryos shown impairments neuronal migration, suggesting that defects radial cortical migration could be involved disease mechanism of dyslexia. Here we present first characterisation...
Developmental dyslexia is a neurodevelopmental disorder that affects reading ability caused by genetic and non-genetic factors. Amongst the susceptibility genes identified to date, KIAA0319 prime candidate. RNA-interference experiments in rats suggested its involvement cortical migration but we could not confirm these findings Kiaa0319-mutant mice. Given homologous gene Kiaa0319L (AU040320) has also been proposed play role neuronal migration, interrogated whether absence of AU040320 alone or...
Abstract Study of knockout (KO) mice has helped understand the link between many genes/proteins and human diseases. Identification infertile KO provides valuable tools to characterize molecular mechanisms underlying gamete formation. The KIAA0319L gene been described have a putative association with dyslexia; surprisingly, we observed that homozygous males for AU040320 , ortholog, are present globozoospermia-like phenotype. Mutant spermatozoa mostly immotile display malformed roundish head...
Abstract Background Vacuolar protein sorting 13 homolog A ( VPS13A ) disease, historically known as chorea‐acanthocytosis, is a rare neurodegenerative disorder caused by biallelic mutations in VPS13A, usually resulting reduced or absent levels of its product, VPS13A. localizes to contact sites between subcellular organelles, consistent with recently identified role lipid transfer membranes. Mutations are associated neuronal loss the striatum, most prominently caudate nucleus, and marked...