Research Topics
Genomes and Genes
| Thomas BraulkeSummaryAffiliation: University of Hamburg Country: Germany Publications
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Detail Information
Publications
Sorting of lysosomal proteinsThomas Braulke
University Medical Center Hamburg Eppendorf, Department Biochemistry, Children s Hospital Research campus, Martinistr 52, 20246, Hamburg, Germany
Biochim Biophys Acta 1793:605-14. 2009..The complex interaction of both luminal and cytosolic signals with recognition proteins guarantees the specific and directed transport of proteins to lysosomes...
Proteolytic processing of the gamma-subunit is associated with the failure to form GlcNAc-1-phosphotransferase complexes and mannose 6-phosphate residues on lysosomal enzymes in human macrophagesSandra Pohl
Department of Biochemistry, Children s Hospital, University Medical Center Hamburg Eppendorf, 20246 Hamburg, Germany
J Biol Chem 285:23936-44. 2010..These findings demonstrate that proteolytic processing of the gamma-subunit represents a novel mechanism to regulate GlcNAc-1-phosphotransferase activity and the subsequent sorting of lysosomal enzymes...- Lysosomal dysfunction causes neurodegeneration in mucolipidosis II 'knock-in' miceK Kollmann
Department of Biochemistry, Children s Hospital, University Medical Center Hamburg Eppendorf, 20246 Hamburg, Germany
Brain 135:2661-75. 2012..These lysosomal proteins might be a potential target for a valid therapeutic approach for mucolipidosis II disease... - Molecular analysis of the GlcNac-1-phosphotransferaseT Braulke
Department of Pediatrics, University Medical Center Hamburg Eppendorf, Hamburg, Germany
J Inherit Metab Dis 31:253-7. 2008..The role of the gamma-subunits for activity, stability and oligomerization of the GlcNac-1-phosphotransferase subunits is still unclear... - Residual activity and proteasomal degradation of p.Ser298Pro sulfamidase identified in patients with a mild clinical phenotype of Sanfilippo A syndromeNicole Muschol
Department of Paediatrics, University Medical Center Hamburg Eppendorf, Germany
Am J Med Genet A 155:1634-9. 2011.... - Analysis of potential biomarkers and modifier genes affecting the clinical course of CLN3 diseaseAnne Hélène Lebrun
Children s Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany
Mol Med 17:1253-61. 2011.... - The mutation p.Ser298Pro in the sulphamidase gene (SGSH) is associated with a slowly progressive clinical phenotype in mucopolysaccharidosis type IIIA (Sanfilippo A syndrome)Ann Meyer
Metabolic Center, Dept of Paediatrics, University Medical Center Hamburg Eppendorf, Hamburg, Germany
Hum Mutat 29:770. 2008..These data suggest that in MPS IIIA patients carrying the mutation p.Ser298Pro a slowly progressive phenotype can be predicted and this may have an important impact on parental counselling and therapeutic interventions... - Lysosomal targeting of the CLN7 membrane glycoprotein and transport via the plasma membrane require a dileucine motifPieter Steenhuis
Department of Biochemistry, Children s Hospital, University Medical Center Hamburg Eppendorf, Martinistr 52, D 20246 Hamburg, Germany
Traffic 11:987-1000. 2010.... - A key enzyme in the biogenesis of lysosomes is a protease that regulates cholesterol metabolismKatrin Marschner
Department of Biochemistry, Children s Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany
Science 333:87-90. 2011..Thus, S1P functions in the biogenesis of lysosomes, and lipid-independent phenotypes of S1P deficiency may be caused by lysosomal dysfunction... - Mannose 6 dephosphorylation of lysosomal proteins mediated by acid phosphatases Acp2 and Acp5Georgia Makrypidi
Department of Biochemistry, Children s Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany
Mol Cell Biol 32:774-82. 2012..The data demonstrate that dephosphorylation of Man6P-containing lysosomal proteins requires the concerted action of Acp2 and Acp5 and is needed for hydrolysis and removal of degradation products... - Accumulation of bis(monoacylglycero)phosphate and gangliosides in mouse models of neuronal ceroid lipofuscinosisSabrina Jabs
University Medical Center Hamburg Eppendorf, Children s Hospital Biochemistry, Hamburg, Germany
J Neurochem 106:1415-25. 2008.... 
A dileucine motif and a cluster of acidic amino acids in the second cytoplasmic domain of the batten disease-related CLN3 protein are required for efficient lysosomal targetingStephan Storch
Department of Biochemistry, Children s Hospital, University of Hamburg, D 20246 Hamburg, Germany
J Biol Chem 279:53625-34. 2004....- Compensatory expression of human N-acetylglucosaminyl-1-phosphotransferase subunits in mucolipidosis type III gammaSandra Pohl
Department of Biochemistry, Children s Hospital, University Medical Center Hamburg Eppendorf Martinistrasse 52, Building N27, 20246 Hamburg, Germany
Biochim Biophys Acta 1792:221-5. 2009..The data suggest that the gamma-subunit is important for the balance of phosphotransferase subunits rather for general binding of lysosomal enzymes... - Disruption of the autophagy-lysosome pathway is involved in neuropathology of the nclf mouse model of neuronal ceroid lipofuscinosisMelanie Thelen
Department of Biochemistry, Children s Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany
PLoS ONE 7:e35493. 2012..These data suggest that proteasomal degradation of mutant Cln6 is sufficient to prevent the accumulation of misfolded Cln6 protein, whereas lysosomal dysfunction impairs constitutive autophagy promoting neurodegeneration... - Pathogenic mutations cause rapid degradation of lysosomal storage disease-related membrane protein CLN6Anna Katherina Kurze
Department of Biochemistry, Children s Hospital, University Hospital Hamburg Eppendorf, Hamburg, Germany
Hum Mutat 31:E1163-74. 2010..Both degradative pathways seem to be sufficient to prevent the accumulation/aggregation of the mutant CLN6 polypeptides in the endoplasmic reticulum... - Missense mutations in N-acetylglucosamine-1-phosphotransferase alpha/beta subunit gene in a patient with mucolipidosis III and a mild clinical phenotypeStephan Tiede
Department of Biochemistry, Children s Hospital, University Hospital Hamburg Eppendorf, Hamburg, Germany
Am J Med Genet A 137:235-40. 2005..The data indicate that defects in genes other than GNPTAG can be linked to ML III contributing to the variability of the phenotype... - Missense mutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTA) in a patient with mucolipidosis II induces changes in the size and cellular distribution of GNPTGStephan Tiede
Department of Biochemistry, Children s Hospital, University Hospital Hamburg Eppendorf, Hamburg, Germany
Hum Mutat 27:830-1. 2006..The data demonstrate that defective GNPTA not only impairs lysosomal enzyme targeting but also the availability of intact GNPTG required for phosphotransferase activity and assembly of subunits... - Disease-causing missense mutations affect enzymatic activity, stability and oligomerization of glutaryl-CoA dehydrogenase (GCDH)Britta Keyser
Department of Biochemistry, Children s Hospital, University Medical Center Hamburg Eppendorf, 20246 Hamburg, Germany
Hum Mol Genet 17:3854-63. 2008..These results indicate that reduced intramitochondrial stability as well as the impaired formation of homo- and heteromeric GCDH complexes can underlie GA1... - Post-translational modifications of the gamma-subunit affect intracellular trafficking and complex assembly of GlcNAc-1-phosphotransferaseMarisa Encarnação
Department of Biochemistry, Children s Hospital, University Medical Center Hamburg Eppendorf, 20246 Hamburg, Germany
J Biol Chem 286:5311-8. 2011..The data provide evidence that assembly of the GlcNAc-1-phosphotransferase complex takes place in the ER and requires dimerization of the γ-subunits... - Increased expression of lysosomal acid phosphatase in CLN3-defective cells and mouse brain tissueSandra Pohl
Department of Biochemistry, Children s Hospital, University Medical Center Hamburg, Hamburg, Germany
J Neurochem 103:2177-88. 2007..The data suggest that lysosomal dysfunction and accumulation of storage material require increased biogenesis of LAP/ACP2 and LAMP-2 positive membranes which makes LAP/ACP2 suitable as biomarker of Batten disease... - Topology and endoplasmic reticulum retention signals of the lysosomal storage disease-related membrane protein CLN6Claudia Heine
Department of Biochemistry, University Hospital Hamburg Eppendorf, Children s Hospital, Hamburg, Germany
Mol Membr Biol 24:74-87. 2007..Additionally, the ability of CLN6 to homodimerize may also prevent exit from the ER via an interaction with membrane-associated factors... - Glutaric aciduria type 1 metabolites impair the succinate transport from astrocytic to neuronal cellsJessica Lamp
Children s Hospital, Department of Biochemistry, University Medical Center Hamburg Eppendorf, 20246 Hamburg, Germany
J Biol Chem 286:17777-84. 2011..These results suggest that elevated levels of GA and 3OHGA may lead to neuronal injury and cell death via disruption of TCA cycle activity... - High expression of disease-related Cln6 in the cerebral cortex, purkinje cells, dentate gyrus, and hippocampal ca1 neuronsMelanie Thelen
Department of Biochemistry, Children s Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany
J Neurosci Res 90:568-74. 2012..These findings implicate Cln6 in the survival and maturation of specific neuronal populations during development and make it possible to compare regional Cln6 expression with the distribution of subsequent pathology... - A novel single-chain antibody fragment for detection of mannose 6-phosphate-containing proteins: application in mucolipidosis type II patients and miceSven Muller-Loennies
University Medical Center Hamburg Eppendorf, Department of Biochemistry, Children s Hospital, Martinistr 52, Bld N27, 20246 Hamburg, Germany
Am J Pathol 177:240-7. 2010..Thus, the single-chain antibody fragment against Man6P was demonstrated to allow the specific, rapid, and convenient detection of Man6P-containing proteins and facilitates the diagnosis of ML II and ML III... - Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferaseStephan Tiede
Department of Biochemistry, Children s Hospital, University of Hamburg, Martinistr 52, 20246 Hamburg, Germany
Nat Med 11:1109-12. 2005..Our results provide evidence that GNPTA encodes a subunit of GlcNAc-1-phosphotransferase defective in individuals with ML II... - Mannose phosphorylation in health and diseaseKatrin Kollmann
Department of Biochemistry, Children s Hospital, University Medical Center Hamburg Eppendorf, Research Campus, Martinistrasse 52, 20246 Hamburg, Germany
Eur J Cell Biol 89:117-23. 2010.... - Glycosylation- and phosphorylation-dependent intracellular transport of lysosomal hydrolasesSandra Pohl
Department of Biochemistry, Children s Hospital, University Medical Center Hamburg Eppendorf, D 20246 Hamburg, Germany
Biol Chem 390:521-7. 2009.... - Loss of N-acetylglucosamine-1-phosphotransferase gamma subunit due to intronic mutation in GNPTG causes mucolipidosis type III gamma: Implications for molecular and cellular diagnosticsSandra Pohl
Department of Biochemistry, Children s Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany
Am J Med Genet A 152:124-32. 2010..These data contribute to an efficient diagnostic strategy to identify Patients with MLIII gamma and characterize their biochemical defect in fibroblasts... - A novel mutation in UDP-N-acetylglucosamine-1-phosphotransferase gamma subunit (GNPTAG) in two siblings with mucolipidosis type III alters a used glycosylation siteStephan Tiede
Department of Biochemistry, Children's Hospital, Hamburg, Germany
Hum Mutat 24:535. 2004..These data suggest that the loss of the used glycosylation site in the gamma subunit may affect the intracellular localization of GNPTAG and the overall efficiency of M6P formation... - Retention of lysosomal protein CLN5 in the endoplasmic reticulum causes neuronal ceroid lipofuscinosis in Asian sibshipAnne Hélène Lebrun
Department of Biochemistry, Children s Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany
Hum Mutat 30:E651-61. 2009..Double immunofluorescence microscopy showed that while the wild-type CLN5 protein is localized in lysosomes, both mutant CLN5 proteins are retained in the endoplasmic reticulum rather than reaching the lysosome... - Interaction of insulin-like growth factor II (IGF-II) with multiple plasma proteins: high affinity binding of plasminogen to IGF-II and IGF-binding protein-3Sandra Oesterreicher
University Hospital Hamburg Eppendorf, Children s Hospital, Department of Biochemistry, Martinistrasse 52, D 20246 Hamburg, Germany
J Biol Chem 280:9994-10000. 2005.... - Scoring evaluation of the natural course of mucopolysaccharidosis type IIIA (Sanfilippo syndrome type A)Ann Meyer
University Medical Center Hamburg Eppendorf, Metabolic Center, Department of Pediatrics, Martinistrasse 52, Building N23, 20246 Hamburg, Germany
Pediatrics 120:e1255-61. 2007..The onset and severity of the disease are highly variable. The purpose of this study was to describe the natural course of mucopolysaccharidosis type IIIA in a large cohort of patients... - Mutational analysis in longest known survivor of mucopolysaccharidosis type VIIStephan Storch
UKE University Hospital, Children s Hospital, University of Hamburg, Martinistrasse 52, Haus W23, 20246 Hamburg, Germany
Hum Genet 112:190-4. 2003..We attribute the mild phenotype to the residual catalytic activity provided by the K350N mutant. At the time of her death at the age of 37 years, this patient was the longest known survivor with MPS VII... - C-terminal prenylation of the CLN3 membrane glycoprotein is required for efficient endosomal sorting to lysosomesStephan Storch
Department of Biochemistry, Children s Hospital, University Hospital Hamburg, Martinistr 52, Bldg W 23, 20246 Hamburg, Germany
Traffic 8:431-44. 2007..The data suggest that co-operative signal structures in different cytoplasmic domains of CLN3 are required for efficient sorting and for transport to the lysosome... - Transport, enzymatic activity, and stability of mutant sulfamidase (SGSH) identified in patients with mucopolysaccharidosis type III ANicole Muschol
Department of Biochemistry, Children s Hospital, University Hospital Hamburg Eppendorf, Hamburg, Germany
Hum Mutat 23:559-66. 2004..571G>A (p.Gly191Arg), c.1297C>T (p.Arg433Trp), c.1026dupC (p.Leu343fsX158), and c.1135delG (p.Val379fsX33) mutant proteins probably occurs in the ER, whereas c.488T>C (p.Leu163Pro) mutant protein showed instability in the lysosomes... - N-glycans and glycosylphosphatidylinositol-anchor act on polarized sorting of mouse PrP(C) in Madin-Darby canine kidney cellsBerta Puig
Institute of Neuropathology, University Medical Center Hamburg Eppendorf, Hamburg, Germany
PLoS ONE 6:e24624. 2011..Exchange of the PrP(C) GPI-anchor for the one of Thy-1 redirects PrP(C) to the apical membrane. In conclusion, both N-glycosylation and GPI-anchor act on polarized sorting of PrP(C), with the GPI-anchor being dominant over N-glycans... - Transport and distribution of 3-hydroxyglutaric acid before and during induced encephalopathic crises in a mouse model of glutaric aciduria type 1Britta Keyser
Children s Hospital, Department of Biochemistry, University Medical Center Hamburg Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
Biochim Biophys Acta 1782:385-90. 2008..The data demonstrate that under conditions mimicking encephalopathic crises the blood-brain barrier appears to remain intact... - Endothelial effects of 3-hydroxyglutaric acid: implications for glutaric aciduria type IChris Mühlhausen
Department of Pediatrics, University of Hamburg, Germany
Pediatr Res 59:196-202. 2006..These data may provide insight in the mechanisms of 3-OH-GA-induced vasculopathic processes and suggest N-methyl-D-aspartate receptor-dependent and -independent pathways in the pathogenesis of GA1... - A replacement of the active-site aspartic acid residue 293 in mouse cathepsin D affects its intracellular stability, processing and transport in HEK-293 cellsSanna Partanen
Children s Hospital Biochemistry, University of Hamburg, Martinistr 52, D 20246 Hamburg, Germany
Biochem J 369:55-62. 2003..These data suggest that the mutation may result in a conformational change which affects stability, processing and transport of the enzyme... - Defective endoplasmic reticulum-resident membrane protein CLN6 affects lysosomal degradation of endocytosed arylsulfatase AClaudia Heine
Department of Biochemistry, Children s Hospital, University of Hamburg, D 20246 Hamburg, Germany
J Biol Chem 279:22347-52. 2004..These data suggest that defects in the ER-resident CLN6 protein lead to lysosomal dysfunctions, which may result in lysosomal accumulation of storage material... - 3-Hydroxyglutaric acid is transported via the sodium-dependent dicarboxylate transporter NaDC3Franziska Stellmer
Department of Pediatrics, University Medical Center Hamburg Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany
J Mol Med (Berl) 85:763-70. 2007..The data demonstrate for the first time the membrane translocation of 3OH-GA mediated by NaDC3 and the cis-inhibitory effect on OCT2-mediated transport of cations... - Isolation and characterization of circulating fragments of the insulin-like growth factor binding protein-3Bernd Kubler
Children s Hospital Biochemistry, University of Hamburg, Martinistr 52, D 20246, Hamburg, Germany
FEBS Lett 518:124-8. 2002..The data indicate that proteolysis of circulating IGFBP-3 occurs in the variable domain at residues alanine 98, phenylalanine 138, glutamine 157, and tyrosine 159...