Schmidt, Bernhard

[["dc.bibliographiccitation.firstpage","710"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Biochimica et Biophysica Acta (BBA) - Molecular Cell Research"],["dc.bibliographiccitation.lastpage","725"],["dc.bibliographiccitation.volume","1793"],["dc.contributor.author","Dierks, Thomas"],["dc.contributor.author","Schlotawa, Lars"],["dc.contributor.author","Frese, Marc-Andre"],["dc.contributor.author","Radhakrishnan, Karthikeyan"],["dc.contributor.author","von Figura, Kurt"],["dc.contributor.author","Schmidt, Bernhard"],["dc.date.accessioned","2018-11-07T08:30:52Z"],["dc.date.available","2018-11-07T08:30:52Z"],["dc.date.issued","2009"],["dc.description.abstract","Multiple sulfatase deficiency (MSD), mucolipidosis (MIL) II/III and Niemann-Pick type C1 (NPC1) disease are rare but fatal lysosomal storage disorders caused by the genetic defect of non-lysosomal proteins. The NPC1 protein mainly localizes to late endosomes and is essential for cholesterol redistribution from endocytosed LDL to cellular membranes. NPC1 deficiency leads to lysosomal accumulation of a broad range of lipids. The precise functional mechanism of this membrane protein, however, remains puzzling. ML II, also termed I cell disease. and the less severe ML III result from deficiencies of the Golgi enzyme N-acetylglucosamine 1-phosphotransferase leading to a global defect of lysosome biogenesis. In patient cells, newly synthesized lysosomal proteins are not equipped with the critical lysosomal trafficking marker mannose 6-phosphate, thus escaping from lysosomal sorting at the trans Golgi network. MSD affects the entire sulfatase family, at least seven members of which are lysosomal enzymes that are specifically involved in the degradation of sulfated glycosaminoglycans, sulfolipids or other sulfated molecules. The combined deficiencies of all sulfatases result from a defective post-translational modification by the ER-localized formylglycine-generating enzyme (FGE), which oxidizes a specific cysteine residue to formylglycine, the catalytic residue enabling a unique mechanism of sulfate ester hydrolysis. This review gives an update on the molecular bases of these enigmatic diseases, which have been challenging researchers since many decades and so far led to a number of surprising findings that give deeper insight into both the cell biology and the pathobiochemistry underlying these complex disorders. In case of MSD, considerable progress has been made in recent years towards an understanding of disease-causing FGE mutations. First approaches to link molecular parameters with clinical manifestation have been described and even therapeutical options have been addressed. Further. the discovery of FGE as an essential sulfatase activating enzyme has considerable impact on enzyme replacement or gene therapy of lysosomal storage disorders caused by single sulfatase deficiencies. (C) 2008 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.bbamcr.2008.11.015"],["dc.identifier.isi","000265369800011"],["dc.identifier.pmid","19124046"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16996"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0167-4889"],["dc.title","Molecular basis of multiple sulfatase deficiency, mucolipidosis II/III and Niemann-Pick C1 disease - Lysosomal storage disorders caused by defects of non-lysosomal proteins"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","142"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurobiology"],["dc.bibliographiccitation.lastpage","161"],["dc.bibliographiccitation.volume","52"],["dc.contributor.author","Kratzke, Manuel"],["dc.contributor.author","Candiello, Ermes"],["dc.contributor.author","Schmidt, Bernhard"],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Schu, Peter"],["dc.date.accessioned","2018-11-07T09:54:05Z"],["dc.date.available","2018-11-07T09:54:05Z"],["dc.date.issued","2015"],["dc.description.abstract","Adaptor protein (AP)-1/sigma 1B(-/-) mice have reduced synaptic-vesicle (SV) recycling and increased endosomes. Mutant mice have impaired spatial memory, and sigma 1B-deficient humans have a severe mental retardation. In order to define these sigma 1B(-/-) 'bulk' endosomes and to determine their functions in SV recycling, we developed a protocol to separate them from the majority of the neuronal endosomes. The sigma 1B(-/-) 'bulk' endosomes proved to be classic early endosomes with an increase in the phospholipid phosphatidylinositol 3-phosphate (PI-3-P), which recruits proteins mediating protein sorting out of early endosomes into different routes. sigma 1B deficiency induced alterations in the endosomal proteome reveals two major functions: SV protein storage and sorting into endolysosomes. Alternative endosomal recycling pathways are not up-regulated, but certain SV proteins are misrouted. Tetraspanins are enriched in sigma 1B(-/-) synaptosomes, but not in their endosomes or in their clathrin-coated-vesicles (CCVs), indicating AP-1/sigma 1B-dependent sorting. Synapses contain also more AP-2 CCV, although it is expected that they contain less due to reduced SV recycling. Coat composition of these AP-2 CCVs is altered, and thus, they represent a subpopulation of AP-2 CCVs. Association of calmodulin-dependent protein kinase (CaMK)-II alpha, -delta and casein kinase (CK)-II alpha with the endosome/SV pool is altered, as well as 14-3-3 eta, indicating changes in specific signalling pathways regulating synaptic plasticity. The accumulation of early endosomes and endocytotic AP-2 CCV indicates the regulation of SV recycling via early endosomes by the interdependent regulation of AP-2-mediated endocytosis and AP-1/sigma 1B-mediated SV reformation."],["dc.description.sponsorship","DFG [Schu 802/3-1, 802/3-2]"],["dc.identifier.doi","10.1007/s12035-014-8852-0"],["dc.identifier.isi","000358341600014"],["dc.identifier.pmid","25128028"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36465"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Humana Press Inc"],["dc.relation.issn","1559-1182"],["dc.relation.issn","0893-7648"],["dc.title","AP-1/sigma 1B-Dependent SV Protein Recycling Is Regulated in Early Endosomes and Is Coupled to AP-2 Endocytosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","970"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.lastpage","975"],["dc.bibliographiccitation.volume","174"],["dc.contributor.author","Roos, Christian"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Schmidt, Bernhard"],["dc.contributor.author","Günther, Eberhard"],["dc.contributor.author","Walter, Lutz"],["dc.date.accessioned","2022-10-06T13:26:53Z"],["dc.date.available","2022-10-06T13:26:53Z"],["dc.date.issued","2005"],["dc.identifier.doi","10.4049/jimmunol.174.2.970"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/115191"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-602"],["dc.relation.eissn","1550-6606"],["dc.relation.issn","0022-1767"],["dc.relation.orgunit","Deutsches Primatenzentrum"],["dc.title","The Rat Expresses Two Complement Factor C4 Proteins, but Only One Isotype Is Expressed in the Liver"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5828"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","5839"],["dc.bibliographiccitation.volume","288"],["dc.contributor.author","Ennemann, Eva C."],["dc.contributor.author","Radhakrishnan, Karthikeyan"],["dc.contributor.author","Mariappan, Malaiyalam"],["dc.contributor.author","Wachs, Michaela"],["dc.contributor.author","Pringle, Thomas H."],["dc.contributor.author","Schmidt, Bernhard"],["dc.contributor.author","Dierks, Thomas"],["dc.date.accessioned","2018-11-07T09:28:01Z"],["dc.date.available","2018-11-07T09:28:01Z"],["dc.date.issued","2013"],["dc.description.abstract","Formylglycine-generating enzyme (FGE) post-translationally converts a specific cysteine in newly synthesized sulfatases to formylglycine (FGly). FGly is the key catalytic residue of the sulfatase family, comprising 17 nonredundant enzymes in human that play essential roles in development and homeostasis. FGE, a resident protein of the endoplasmic reticulum, is also secreted. A major fraction of secreted FGE is N-terminally truncated, lacking residues 34-72. Here we demonstrate that this truncated form is generated intracellularly by limited proteolysis mediated by proprotein convertase(s) (PCs) along the secretory pathway. The cleavage site is represented by the sequence RYSR72 down arrow, a motif that is conserved in higher eukaryotic FGEs, implying important functionality. Residues Arg-69 and Arg-72 are critical because their mutation abolishes FGE processing. Furthermore, residues Tyr-70 and Ser-71 confer an unusual property to the cleavage motif such that endogenous as well as overexpressed FGE is only partially processed. FGE is cleaved by furin, PACE4, and PC5a. Processing is disabled in furin-deficient cells but fully restored upon transient furin expression, indicating that furin is the major protease cleaving FGE. Processing by endogenous furin occurs mostly intracellularly, although also extracellular processing is observed in HEK293 cells. Interestingly, the truncated form of secreted FGE no longer possesses FGly-generating activity, whereas the unprocessed form of secreted FGE is active. As always both forms are secreted, we postulate that furin-mediated processing of FGE during secretion is a physiological means of higher eukaryotic cells to regulate FGE activity upon exit from the endoplasmic reticulum."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [DI 575/7, SCHM 830/2, SFB 860]"],["dc.identifier.doi","10.1074/jbc.M112.405159"],["dc.identifier.isi","000315342500053"],["dc.identifier.pmid","23288839"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30675"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.title","Proprotein Convertases Process and Thereby Inactivate Formylglycine-generating Enzyme"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3473"],["dc.bibliographiccitation.issue","18"],["dc.bibliographiccitation.journal","Molecular and Cellular Biology"],["dc.bibliographiccitation.lastpage","3485"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Melin, Jonathan"],["dc.contributor.author","Schulz, Christian"],["dc.contributor.author","Wrobel, Lidia"],["dc.contributor.author","Bernhard, Olaf"],["dc.contributor.author","Chacinska, Agnieszka"],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Schmidt, Bernhard"],["dc.contributor.author","Rehling, Peter"],["dc.date.accessioned","2017-09-07T11:45:36Z"],["dc.date.available","2017-09-07T11:45:36Z"],["dc.date.issued","2014"],["dc.description.abstract","More than 70% of mitochondrial proteins utilize N-terminal presequences as targeting signals. Presequence interactions with redundant cytosolic receptor domains of the translocase of the outer mitochondrial membrane (TOM) are well established. However, after the presequence enters the protein-conducting Tom40 channel, the recognition events that occur at the trans side leading up to the engagement of the presequence with inner membrane-bound receptors are less well defined. Using a photoaffinity-labeling approach with modified presequence peptides, we identified Tom40 as a presequence interactor of the TOM complex. Utilizing mass spectrometry, we mapped Tom40's presequence-interacting regions to both sides of the beta-barrel. Analysis of a phosphorylation site within one of the presequence-interacting regions revealed altered translocation kinetics along the presequence pathway. Our analyses assess the relation between the identified presequence-binding region of Tom40 and the intermembrane space domain of Tom22. The identified presequence-interacting region of Tom40 is capable of functioning independently of the established trans-acting TOM presequence-binding domain during matrix import."],["dc.identifier.doi","10.1128/MCB.00433-14"],["dc.identifier.gro","3142065"],["dc.identifier.isi","000341024900010"],["dc.identifier.pmid","25002531"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4156"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1098-5549"],["dc.relation.issn","0270-7306"],["dc.title","Presequence Recognition by the Tom40 Channel Contributes to Precursor Translocation into the Mitochondrial Matrix"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","425"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms"],["dc.bibliographiccitation.lastpage","435"],["dc.bibliographiccitation.volume","1829"],["dc.contributor.author","Xu, X."],["dc.contributor.author","Tan, Xiaoying"],["dc.contributor.author","Lin, Qiong"],["dc.contributor.author","Schmidt, Bernhard"],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.date.accessioned","2018-11-07T09:25:29Z"],["dc.date.available","2018-11-07T09:25:29Z"],["dc.date.issued","2013"],["dc.description.abstract","Dazl (deleted in azoospermia-like) is an RNA binding protein that is important for germ cell differentiation in vertebrates. In the present study, we report the identification of a novel Dazl isoform (Dazl_Delta 8) that results from alternative splicing of exon8 of mouse Dazl. We observed the expression of Dazl_Delta 8 in various pluripotent cell types, but not in somatic cells. Furthermore, the Dazl_Delta 8 splice variant was expressed along with the full-length isoform of Dazl (Dazl_FL) throughout male germ-cell development and in the ovary. Sub-cellular localization studies of Dazl_Delta 8 revealed a diffused cytoplasmic and large granular pattern, which is similar to the localization patterns of Dazl_FL protein. In contrast to the well documented translation stimulation function in germ cells, overexpression and downregulation studies of Dazl isoforms (Dazl_FL and Dazl_Delta 8) revealed a role for Dazl in the negative translational regulation, of Mvh, a known target of Dazl, as well as Oct3/4 and Sox2 in embryonic stem cells (ESCs). In line with these observations, a luciferase reporter assay with the 3'UTRs of Oct3/4 and Mvh confirmed the translational repressive role of Dazl isoforms in ESCs but not in germ cells derived cell line GC-1. Further, we identified several putative target mRNAs of Dazl_FL and Dazl_Delta 8 in ESCs through RNA-binding immunoprecipitation followed by whole genome transcriptome analysis. Collectively, our results show a translation repression function of Dazl in pluripotent stem cells. (C) 2013 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.bbagrm.2012.12.010"],["dc.identifier.isi","000318134500001"],["dc.identifier.pmid","23298641"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30075"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1874-9399"],["dc.title","Mouse Dazl and its novel splice variant functions in translational repression of target mRNAs in embryonic stem cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","11556"],["dc.bibliographiccitation.issue","17"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","11564"],["dc.bibliographiccitation.volume","283"],["dc.contributor.author","Mariappan, Malaiyalam"],["dc.contributor.author","Gande, Santosh Lakshmi"],["dc.contributor.author","Radhakrishnan, Karthikeyan"],["dc.contributor.author","Schmidt, Bernhard"],["dc.contributor.author","Dierks, Thomas"],["dc.contributor.author","von Figura, Kurt"],["dc.date.accessioned","2018-11-07T11:15:58Z"],["dc.date.available","2018-11-07T11:15:58Z"],["dc.date.issued","2008"],["dc.description.abstract","Formylglycine-generating enzyme (FGE) catalyzes the oxidation of a specific cysteine residue in nascent sulfatase polypeptides to formylglycine (FGly). This FGly is part of the active site of all sulfatases and is required for their catalytic activity. Here we demonstrate that residues 34-68 constitute an N-terminal extension of the FGE catalytic core that is dispensable for in vitro enzymatic activity of FGE but is required for its in vivo activity in the endoplasmic reticulum (ER), i.e. for generation of FGly residues in nascent sulfatases. In addition, this extension is needed for the retention of FGE in the ER. Fusing a KDEL retention signal to the C terminus of FGE is sufficient to mediate retention of an N-terminally truncated FGE but not sufficient to restore its biological activity. Fusion of FGE residues 1-88 to secretory proteins resulted in ER retention of the fusion protein. Moreover, when fused to the paralog of FGE (pFGE), which itself lacks FGly-generating activity, the FGE extension ( residues 34-88) of this hybrid construct led to partial restoration of the biological activity of co-expressed N-terminally truncated FGE. Within the FGE N-terminal extension cysteine 52 is critical for the biological activity. We postulate that this N-terminal region of FGE mediates the interaction with an ER component to be identified and that this interaction is required for both the generation of FGly residues in nascent sulfatase polypeptides and for retention of FGE in the ER."],["dc.identifier.doi","10.1074/jbc.M707858200"],["dc.identifier.isi","000255067400056"],["dc.identifier.pmid","18305113"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54486"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.title","The non-catalytic N-terminal extension of formylglycine-generating enzyme is required for its biological activity and retention in the endoplasmic reticulum"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","15180"],["dc.bibliographiccitation.issue","15"],["dc.bibliographiccitation.journal","Journal of biological chemistry"],["dc.bibliographiccitation.lastpage","15187"],["dc.bibliographiccitation.volume","280"],["dc.contributor.author","Dickmanns, A."],["dc.contributor.author","Schmidt, Bernhard"],["dc.contributor.author","Rudolph, M."],["dc.contributor.author","Mariappan, M."],["dc.contributor.author","Dierks, T."],["dc.contributor.author","Von Figura, K."],["dc.contributor.author","Ficner, R."],["dc.date.accessioned","2017-09-07T11:54:29Z"],["dc.date.available","2017-09-07T11:54:29Z"],["dc.date.issued","2005"],["dc.description.abstract","In eukaryotes, sulfate esters are degraded by sulfatases, which possess a unique C alpha-formylglycine residue in their active site. The defect in post-translational formation of the C alpha-formylglycine residue causes a severe lysosomal storage disorder in humans. Recently, FGE (formylglycine-generating enzyme) has been identified as the protein required for this specific modification. Using sequence comparisons, a protein homologous to FGE was found and denoted pFGE (paralog of FGE). pFGE binds a sulfatase-derived peptide bearing the FGE recognition motif, but it lacks formylglycine-generating activity. Both proteins belong to a large family of pro- and eukaryotic proteins containing the DUF323 domain, a formylglycine-generating enzyme domain of unknown three-dimensional structure. We have crystallized the glycosylated human pFGE and determined its crystal structure at a resolution of 1.86 angstrom. The structure reveals a novel fold, which we denote the FGE fold and which therefore serves as a paradigm for the DUF323 domain. It is characterized by an asymmetric partitioning of secondary structure elements and is stabilized by two calcium cations. A deep cleft on the surface of pFGE most likely represents the sulfatase polypeptide binding site. The asymmetric unit of the pFGE crystal contains a homodimer. The putative peptide binding site is buried between the monomers, indicating a biological significance of the dimer. The structure suggests the capability of pFGE to form a heterodimer with FGE."],["dc.identifier.doi","10.1074/jbc.M414317200"],["dc.identifier.gro","3143864"],["dc.identifier.isi","000228236800102"],["dc.identifier.pmid","15687489"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1425"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0021-9258"],["dc.title","Crystal structure of human pFGE, the paralog of the C alpha-formylglycine-generating enzyme"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5009"],["dc.bibliographiccitation.issue","24"],["dc.bibliographiccitation.journal","Molecular and Cellular Biology"],["dc.bibliographiccitation.lastpage","5021"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Reinhold, Robert"],["dc.contributor.author","Krüger, Vivien"],["dc.contributor.author","Meinecke, Michael"],["dc.contributor.author","Schulz, Christian"],["dc.contributor.author","Schmidt, Bernhard"],["dc.contributor.author","Grunau, Silke D."],["dc.contributor.author","Guiard, Bernard"],["dc.contributor.author","Wiedemann, Nils"],["dc.contributor.author","van der Laan, Martin"],["dc.contributor.author","Wagner, Richard"],["dc.contributor.author","Rehling, Peter"],["dc.contributor.author","Dudek, Jan"],["dc.date.accessioned","2017-09-07T11:48:21Z"],["dc.date.available","2017-09-07T11:48:21Z"],["dc.date.issued","2012"],["dc.description.abstract","The majority of multispanning inner mitochondrial membrane proteins utilize internal targeting signals, which direct them to the carrier translocase (TIM22 complex), for their import. MPV17 and its Saccharomyces cerevisiae orthologue Sym1 are multispanning inner membrane proteins of unknown function with an amino-terminal presequence that suggests they may be targeted to the mitochondria. Mutations affecting MPV17 are associated with mitochondrial DNA depletion syndrome (MDDS). Reconstitution of purified Sym1 into planar lipid bilayers and electrophysiological measurements have demonstrated that Sym1 forms a membrane pore. To address the biogenesis of Sym1, which oligomerizes in the inner mitochondrial membrane, we studied its import and assembly pathway. Sym1 forms a transport intermediate at the translocase of the outer membrane (TOM) complex. Surprisingly, Sym1 was not transported into mitochondria by an amino-terminal signal, and in contrast to what has been observed in carrier proteins, Sym1 transport and assembly into the inner membrane were independent of small translocase of mitochondrial inner membrane (TIM) and TIM22 complexes. Instead, Sym1 required the presequence of translocase for its biogenesis. Our analyses have revealed a novel transport mechanism for a polytopic membrane protein in which internal signals direct the precursor into the inner membrane via the TIM23 complex, indicating a presequence-independent function of this translocase."],["dc.identifier.doi","10.1128/MCB.00843-12"],["dc.identifier.gro","3142435"],["dc.identifier.isi","000311492200011"],["dc.identifier.pmid","23045398"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8252"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0270-7306"],["dc.title","The Channel-Forming Sym1 Protein Is Transported by the TIM23 Complex in a Presequence-Independent Manner"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1020"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","European Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","1023"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Schlotawa, Lars"],["dc.contributor.author","Radhakrishnan, Karthikeyan"],["dc.contributor.author","Baumgartner, Matthias"],["dc.contributor.author","Schmid, Regula"],["dc.contributor.author","Schmidt, Bernhard"],["dc.contributor.author","Dierks, Thomas"],["dc.contributor.author","Gärtner, Jutta"],["dc.date.accessioned","2017-09-07T11:47:37Z"],["dc.date.available","2017-09-07T11:47:37Z"],["dc.date.issued","2013"],["dc.description.abstract","Multiple sulfatase deficiency (MSD) is a rare inborn error of metabolism affecting posttranslational activation of sulfatases by the formylglycine generating enzyme (FGE). Due to mutations in the encoding SUMF1 gene, FGE's catalytic capacity is impaired resulting in reduced cellular sulfatase activities. Both, FGE protein stability and residual activity determine disease severity and have previously been correlated with the clinical MSD phenotype. Here, we report a patient with a late infantile severe course of disease. The patient is compound heterozygous for two so far undescribed SUMF1 mutations, c.156delC (p.C52fsX57) and c.390A>T (p.E130D). In patient fibroblasts, mRNA of the frameshift allele is undetectable. In contrast, the allele encoding FGE-E130D is expressed. FGE-E130D correctly localizes to the endoplasmic reticulum and has a very high residual molecular activity in vitro (55% of wildtype FGE); however, it is rapidly degraded. Thus, despite substantial residual enzyme activity, protein instability determines disease severity, which highlights that potential MSD treatment approaches should target protein folding and stabilization mechanisms."],["dc.identifier.doi","10.1038/ejhg.2012.291"],["dc.identifier.gro","3142298"],["dc.identifier.isi","000323281400021"],["dc.identifier.pmid","23321616"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6731"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Deutsche Forschungsgemeinschaft; Fonds der Chemischen Industrie"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1018-4813"],["dc.title","Rapid degradation of an active formylglycine generating enzyme variant leads to a late infantile severe form of multiple sulfatase deficiency"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]