Saftig, Paul

[["dc.bibliographiccitation.firstpage","280"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Cellular and Molecular Medicine"],["dc.bibliographiccitation.lastpage","295"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Schneede, Alexander"],["dc.contributor.author","Schmidt, Christine K."],["dc.contributor.author","Hoelttae-Vuori, Maarit"],["dc.contributor.author","Heeren, Joerg"],["dc.contributor.author","Willenborg, Marion"],["dc.contributor.author","Blanz, Judith"],["dc.contributor.author","Domanskyy, Mykola"],["dc.contributor.author","Breiden, Bernadette"],["dc.contributor.author","Brodesser, Susanne"],["dc.contributor.author","Landgrebe, Jobst"],["dc.contributor.author","Sandhoff, Konrad"],["dc.contributor.author","Ikonen, Elina"],["dc.contributor.author","Saftig, Paul"],["dc.contributor.author","Eskelinen, Eeva-Liisa"],["dc.date.accessioned","2018-11-07T08:59:48Z"],["dc.date.available","2018-11-07T08:59:48Z"],["dc.date.issued","2011"],["dc.description.abstract","The mechanisms of endosomal and lysosomal cholesterol traffic are still poorly understood. We showed previously that unesterified cholesterol accumulates in the late endosomes and lysosomes of fibroblasts deficient in both lysosome associated membrane protein-2 (LAMP-2) and LAMP-1, two abundant membrane proteins of late endosomes and lysosomes. In this study we show that in cells deficient in both LAMP-1 and LAMP-2 (LAMP(-/-)), low-density lipoprotein (LDL) receptor levels and LDL uptake are increased as compared to wild-type cells. However, there is a defect in esterification of both endogenous and LDL cholesterol. These results suggest that LAMP(-/-) cells have a defect in cholesterol transport to the site of esterification in the endoplasmic reticulum, likely due to defective export of cholesterol out of late endosomes or lysosomes. We also show that cholesterol accumulates in LAMP-2 deficient liver and that overexpression of LAMP-2 retards the lysosomal cholesterol accumulation induced by U18666A. These results point to a critical role for LAMP-2 in endosomal/lysosomal cholesterol export. Moreover, the late endosomal/lysosomal cholesterol accumulation in LAMP(-/-) cells was diminished by overexpression of any of the three isoforms of LAMP-2, but not by LAMP-1. The LAMP-2 luminal domain, the membrane-proximal half in particular, was necessary and sufficient for the rescue effect. Taken together, our results suggest that LAMP-2, its luminal domain in particular, plays a critical role in endosomal cholesterol transport and that this is distinct from the chaperone-mediated autophagy function of LAMP-2."],["dc.identifier.doi","10.1111/j.1582-4934.2009.00973.x"],["dc.identifier.isi","000287749000010"],["dc.identifier.pmid","19929948"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23996"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1582-1838"],["dc.title","Role for LAMP-2 in endosomal cholesterol transport"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","41"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Experimental Medicine"],["dc.bibliographiccitation.lastpage","58"],["dc.bibliographiccitation.volume","210"],["dc.contributor.author","Schneppenheim, Janna"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Huettl, Susann"],["dc.contributor.author","Luellmann-Rauch, Renate"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Eskelinen, Eeva-Liisa"],["dc.contributor.author","Hermans-Borgmeyer, Irm"],["dc.contributor.author","Fluhrer, Regina"],["dc.contributor.author","Saftig, Paul"],["dc.contributor.author","Schroeder, Bernd"],["dc.date.accessioned","2018-11-07T09:29:12Z"],["dc.date.available","2018-11-07T09:29:12Z"],["dc.date.issued","2013"],["dc.description.abstract","Regulated intramembrane proteolysis is a central cellular process involved in signal transduction and membrane protein turnover. The presenilin homologue signal-peptide-peptidase-like 2a (SPPL2a) has been implicated in the cleavage of type 2 transmembrane proteins. We show that the invariant chain (li, CD74) of the major histocompatability class II complex (MHCII) undergoes intramembrane proteolysis mediated by SPPL2a. B lymphocytes of SPPL2a(-/-) mice accumulate an N-terminal fragment (NTF) of CD74, which severely impairs membrane traffic within the endocytic system and leads to an altered response to B cell receptor stimulation, reduced BAFF-R surface expression, and accumulation of MHCII in transitional developmental stage T1 B cells. This results in significant loss of B cell subsets beyond the T1 stage and disrupted humoral immune responses, which can be recovered by additional ablation of CD74. Hence, we provide evidence that regulation of CD74-NTF levels by SPPL2a is indispensable for B cell development and function by maintaining trafficking and integrity of MHCII-containing endosomes, highlighting SPPL2a as a promising pharmacological target for depleting and/or modulating B cells."],["dc.identifier.isi","000313560900006"],["dc.identifier.pmid","23267015"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30966"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Rockefeller Univ Press"],["dc.relation.issn","0022-1007"],["dc.title","The intramembrane protease SPPL2a promotes B cell development and controls endosomal traffic by cleavage of the invariant chain"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","902"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.lastpage","906"],["dc.bibliographiccitation.volume","406"],["dc.contributor.author","Tanaka, Yoshitaka"],["dc.contributor.author","Guhde, Gundula"],["dc.contributor.author","Suter, Anke"],["dc.contributor.author","Eskelinen, Eeva-Liisa"],["dc.contributor.author","Hartmann, Dieter"],["dc.contributor.author","Lüllmann-Rauch, Renate"],["dc.contributor.author","Blanz, Judith"],["dc.contributor.author","Figura, Kurt von"],["dc.contributor.author","Saftig, Paul"],["dc.contributor.author","Janssen, Paul M. L."],["dc.date.accessioned","2019-07-10T08:12:47Z"],["dc.date.available","2019-07-10T08:12:47Z"],["dc.date.issued","2000"],["dc.description.abstract","Lysosome-associated membrane protein-2 (LAMP-2) is a highly glycosylated protein and an important constituent of the lysosomal membrane1–7. Here we show that LAMP-2 deficiency in mice increases mortality between 20 and 40 days of age. The surviving mice are fertile and have an almost normal life span. Ultrastructurally, there is extensive accumulation of autophagic vacuoles in many tissues including liver, pancreas, spleen, kidney and skeletal and heart muscle. In hepatocytes, the autophagic degradation of long-lived proteins is severely impaired. Cardiac myocytes are ultrastructurally abnormal and heart contractility is severely reduced. These findings indicate that LAMP-2 is critical for autophagy. This theory is further substantiated by the finding that human LAMP-2 deficiency8 causing Danon’s disease is associated with the accumulation of autophagic material in striated myocytes."],["dc.format.mimetype","application/pdf"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?goescholar/3447"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61036"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.notes.status","zu prüfen"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0028-0836"],["dc.rights","Goescholar"],["dc.rights.access","openAccess"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject","autophagic vacuoles; cardiomyopathy; LAMP-2-deficient mice"],["dc.subject.ddc","610"],["dc.title","Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]