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Schu, Peter Valentin
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Schu, Peter Valentin
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Schu, Peter Valentin
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Schu, Peter V.
Schu, P. V.
Schu, Peter
Schu, P.
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2015Journal Article [["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"]]Details DOI PMID PMC WOS2014Journal Article [["dc.bibliographiccitation.firstpage","3477"],["dc.bibliographiccitation.issue","16"],["dc.bibliographiccitation.journal","Journal of Cell Science"],["dc.bibliographiccitation.lastpage","3487"],["dc.bibliographiccitation.volume","127"],["dc.contributor.author","Baltes, Jennifer"],["dc.contributor.author","Larsen, Jakob Vejby"],["dc.contributor.author","Radhakrishnan, Karthikeyan"],["dc.contributor.author","Geumann, Constanze"],["dc.contributor.author","Kratzke, Manuel"],["dc.contributor.author","Petersen, Claus Munck"],["dc.contributor.author","Schu, Peter"],["dc.date.accessioned","2018-11-07T09:36:33Z"],["dc.date.available","2018-11-07T09:36:33Z"],["dc.date.issued","2014"],["dc.description.abstract","Here, we describe altered sorting of sortilin in adipocytes deficient for the sigma 1B-containing AP-1 complex, leading to the inhibition of adipogenesis. The AP-1 complex mediates protein sorting between the trans-Golgi network and endosomes. Vertebrates express three AP1 sigma 1 subunit isoforms - sigma 1A, sigma 1B and sigma 1C (also known as AP1S1, AP1S2 and AP1S3, respectively). sigma 1B-deficient mice display impaired recycling of synaptic vesicles and lipodystrophy. Here, we show that sortilin is overexpressed in adipose tissue from sigma 1B(-/-) mice, and that its overexpression in wild-type cells is sufficient to suppress adipogenesis. sigma 1B-specific binding of sortilin requires the sortilin DxxD-x12-DSxxxL motif. sigma 1B deficiency does not lead to a block of sortilin transport out of a specific organelle, but the fraction that reaches lysosomes is reduced. Sortilin binds to the receptor DLK1, an inhibitor of adipocyte differentiation, and the overexpression of sortilin prevents DLK1 downregulation, leading to enhanced inhibition of adipogenesis. DLK1 and sortilin expression are not increased in the brain tissue of sigma 1B(-/-) mice, although this is the tissue with the highest expression of sigma 1B and sortilin. Thus, adipose-tissue-specific and sigma 1B-dependent routes for the transport of sortilin exist and are involved in the regulation of adipogenesis and adipose-tissue mass."],["dc.identifier.doi","10.1242/jcs.146886"],["dc.identifier.isi","000341180000008"],["dc.identifier.pmid","24928897"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32644"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Company Of Biologists Ltd"],["dc.relation.issn","1477-9137"],["dc.relation.issn","0021-9533"],["dc.title","sigma 1B adaptin regulates adipogenesis by mediating the sorting of sortilin in adipose tissue"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2016Journal Article [["dc.bibliographiccitation.artnumber","29950"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Candiello, Ermes"],["dc.contributor.author","Kratzke, Manuel"],["dc.contributor.author","Wenzel, Dirk"],["dc.contributor.author","Cassel, Dan"],["dc.contributor.author","Schu, Peter"],["dc.date.accessioned","2018-11-07T10:11:38Z"],["dc.date.available","2018-11-07T10:11:38Z"],["dc.date.issued","2016"],["dc.description.abstract","The sigma 1 subunit of the AP-1 clathrin-coated-vesicle adaptor-protein complex is expressed as three isoforms. Tissues express sigma 1A and one of the sigma 1B and sigma 1C isoforms. Brain is the tissue with the highest sigma 1A and sigma 1B expression. sigma 1B-deficiency leads to severe mental retardation, accumulation of early endosomes in synapses and fewer synaptic vesicles, whose recycling is slowed down. AP-1/sigma 1A and AP-1/sigma 1B regulate maturation of these early endosomes into multivesicular body late endosomes, thereby controlling synaptic vesicle protein transport into a degradative pathway. sigma 1A binds ArfGAP1, and with higher affinity brain-specific ArfGAP1, which bind Rabex-5. AP-1/sigma 1A-ArfGAP1-Rabex-5 complex formation leads to more endosomal Rabex-5 and enhanced, Rab5(GTP)-stimulated Vps34 PI3-kinase activity, which is essential for multivesicular body endosome formation. Formation of AP-1/sigma 1A-ArfGAP1-Rabex-5 complexes is prevented by sigma 1B binding of Rabex-5 and the amount of endosomal Rabex-5 is reduced. AP-1 complexes differentially regulate endosome maturation and coordinate protein recycling and degradation, revealing a novel molecular mechanism by which they regulate protein transport besides their established function in clathrin-coated-vesicle formation."],["dc.description.sponsorship","DFG [Schu 802/3-1, Schu 802/3-2, Schu 802/3-4]; GGNB grants"],["dc.identifier.doi","10.1038/srep29950"],["dc.identifier.isi","000379692700001"],["dc.identifier.pmid","27411398"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13532"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40086"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","AP-1/sigma 1A and AP-1/sigma 1B adaptor-proteins differentially regulate neuronal early endosome maturation via the Rab5/Vps34-pathway"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2010Journal Article [["dc.bibliographiccitation.firstpage","1318"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","The EMBO Journal"],["dc.bibliographiccitation.lastpage","1330"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Glyvuk, Nataliya"],["dc.contributor.author","Tsytsyura, Yaroslav"],["dc.contributor.author","Geumann, Constanze"],["dc.contributor.author","D'Hooge, Rudi"],["dc.contributor.author","Hueve, Jana"],["dc.contributor.author","Kratzke, Manuel"],["dc.contributor.author","Baltes, Jennifer"],["dc.contributor.author","Boening, Daniel"],["dc.contributor.author","Klingauf, Juergen"],["dc.contributor.author","Schu, Peter"],["dc.date.accessioned","2018-11-07T08:43:59Z"],["dc.date.available","2018-11-07T08:43:59Z"],["dc.date.issued","2010"],["dc.description.abstract","Synaptic vesicle recycling involves AP-2/clathrin-mediated endocytosis, but it is not known whether the endosomal pathway is also required. Mice deficient in the tissue-specific AP-1-sigma 1B complex have impaired synaptic vesicle recycling in hippocampal synapses. The ubiquitously expressed AP-1-sigma 1A complex mediates protein sorting between the trans-Golgi network and early endosomes. Vertebrates express three sigma 1 subunit isoforms: A, B and C. The expressions of sigma 1A and sigma 1B are highest in the brain. Synaptic vesicle reformation in cultured neurons from sigma 1B-deficient mice is reduced upon stimulation, and large endosomal intermediates accumulate. The sigma 1B-deficient mice have reduced motor coordination and severely impaired long-term spatial memory. These data reveal a molecular mechanism for a severe human X-chromosome-linked mental retardation. The EMBO Journal (2010) 29, 1318-1330. doi: 10.1038/emboj.2010.15; Published online 4 March 2010"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [SFB 523 A6, SFB 523 B10]"],["dc.identifier.doi","10.1038/emboj.2010.15"],["dc.identifier.isi","000276927000003"],["dc.identifier.pmid","20203623"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20103"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0261-4189"],["dc.title","AP-1/sigma 1B-adaptin mediates endosomal synaptic vesicle recycling, learning and memory"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2017Journal Article [["dc.bibliographiccitation.firstpage","356"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","European Journal of Cell Biology"],["dc.bibliographiccitation.lastpage","368"],["dc.bibliographiccitation.volume","96"],["dc.contributor.author","Zizioli, Daniela"],["dc.contributor.author","Geumann, Constanze"],["dc.contributor.author","Kratzke, Manuel"],["dc.contributor.author","Mishra, Ratnakar"],["dc.contributor.author","Borsani, Guiseppe"],["dc.contributor.author","Finazzi, Dario"],["dc.contributor.author","Candiello, Ermes"],["dc.contributor.author","Schu, Peter"],["dc.date.accessioned","2018-11-07T10:22:53Z"],["dc.date.available","2018-11-07T10:22:53Z"],["dc.date.issued","2017"],["dc.description.abstract","gamma 2 adaptin is homologous to gamma 1, but is only expressed in vertebrates while gamma 1 is found in all eukaryotes. We know little about gamma 2 functions and their relation to gamma 1. gamma 1 is an adaptin of the heterotetrameric AP-1 complexes, which sort proteins in and do form clathrin-coated transport vesicles and they also regulate maturation of early endosomes. gamma 1 knockout mice develop only to blastocysts and thus gamma 2 does not compensate gamma 1-deficiency in development. gamma 2 has not been classified as a clathrin-coated vesicle adaptor protein in proteome analyses and functions for monomeric gamma 2 in endosomal protein sorting have been proposed, but adaptin interaction studies suggested formation of heterotetrameric AP-1/gamma 2 complexes. We detected gamma 2 at the trans-Golgi network, on peripheral vesicles and identified gamma 2 clathrin-coated vesicles in mice. Ubiquitous sigma 1A and tissue-specific sigma 1B adaptins bind gamma 2 and gamma 1. sigma 1B knockout in mice does not effect gamma 1/sigma 1A AP-1 levels, but gamma 2/sigma 1A AP-1 levels are increased in brain and adipocytes. Also gamma 2 is essential in development. In zebrafish AP-1/gamma 2 and AP-1/gamma 1 fulfill different, essential functions in brain and the vascular system. (C) 2017 Elsevier GmbH. All rights reserved."],["dc.identifier.doi","10.1016/j.ejcb.2017.03.008"],["dc.identifier.isi","000404504700007"],["dc.identifier.pmid","28372831"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42353"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Gmbh, Urban & Fischer Verlag"],["dc.relation.issn","1618-1298"],["dc.relation.issn","0171-9335"],["dc.title","gamma 2 and gamma 1AP-1 complexes: Different essential functions and regulatory mechanisms in clathrin-dependent protein sorting"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI PMID PMC WOS2010Journal Article [["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","The EMBO Journal"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Glyvuk, Nataliya"],["dc.contributor.author","Tsytsyura, Yaroslav"],["dc.contributor.author","Geumann, Constanze"],["dc.contributor.author","D'Hooge, Rudi"],["dc.contributor.author","Hueve, Jana"],["dc.contributor.author","Kratzke, Manuel"],["dc.contributor.author","Baltes, Jennifer"],["dc.contributor.author","Boening, Daniel"],["dc.contributor.author","Klingauf, Juergen"],["dc.contributor.author","Schu, Peter"],["dc.date.accessioned","2018-11-07T08:42:20Z"],["dc.date.available","2018-11-07T08:42:20Z"],["dc.date.issued","2010"],["dc.format.extent","1941"],["dc.identifier.doi","10.1038/emboj.2010.96"],["dc.identifier.isi","000278235100015"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19673"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0261-4189"],["dc.title","AP-1/sigma 1B-adaptin mediates endosomal synaptic vesicle recycling, learning and memory (vol 29, pg 1318, 2010)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]Details DOI WOS