Wenzel, Dirk

[["dc.bibliographiccitation.firstpage","2292"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Molecular Biology of the Cell"],["dc.bibliographiccitation.lastpage","2301"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Stoldt, Stefan"],["dc.contributor.author","Wenzel, Dirk"],["dc.contributor.author","Hildenbeutel, Markus"],["dc.contributor.author","Wurm, Christian Andreas"],["dc.contributor.author","Herrmann, Johannes M."],["dc.contributor.author","Jakobs, Stefan"],["dc.date.accessioned","2017-09-07T11:48:51Z"],["dc.date.available","2017-09-07T11:48:51Z"],["dc.date.issued","2012"],["dc.description.abstract","The Oxa1 protein is a well-conserved integral protein of the inner membrane of mitochondria. It mediates the insertion of both mitochondrial-and nuclear-encoded proteins from the matrix into the inner membrane. We investigated the distribution of budding yeast Oxa1 between the two subdomains of the contiguous inner membrane-the cristae membrane (CM) and the inner boundary membrane (IBM)-under different physiological conditions. We found that under fermentable growth conditions, Oxa1 is enriched in the IBM, whereas under nonfermentable (respiratory) growth conditions, it is predominantly localized in the CM. The enrichment of Oxa1 in the CM requires mitochondrial translation; similarly, deletion of the ribosome-binding domain of Oxa1 prevents an enrichment of Oxa1 in the CM. The predominant localization in the IBM under fermentable growth conditions is prevented by inhibiting mitochondrial protein import. Furthermore, overexpression of the nuclear-encoded Oxa1 substrate Mdl1 shifts the distribution of Oxa1 toward the IBM. Apparently, the availability of nuclear- and mitochondrial-encoded substrates influences the inner-membrane distribution of Oxa1. Our findings show that the distribution of Oxa1 within the inner membrane is dynamic and adapts to different physiological needs."],["dc.identifier.doi","10.1091/mbc.E11-06-0538"],["dc.identifier.gro","3142518"],["dc.identifier.isi","000306286700006"],["dc.identifier.pmid","22513091"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9497"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8878"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1059-1524"],["dc.rights","CC BY-NC-SA 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-sa/3.0"],["dc.title","The inner-mitochondrial distribution of Oxa1 depends on the growth conditions and on the availability of substrates"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1576"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Leukemia"],["dc.bibliographiccitation.lastpage","1586"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Chapuy, Björn"],["dc.contributor.author","Koch, R."],["dc.contributor.author","Radunski, Ulf"],["dc.contributor.author","Corsham, Sabrina"],["dc.contributor.author","Cheong, Naeun"],["dc.contributor.author","Inagaki, Nobuya"],["dc.contributor.author","Ban, N."],["dc.contributor.author","Wenzel, D."],["dc.contributor.author","Reinhardt, D."],["dc.contributor.author","Zapf, Antonia"],["dc.contributor.author","Schweyer, Stefan"],["dc.contributor.author","Kosari, F."],["dc.contributor.author","Klapper, Wolfram"],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Wulf, Gerald G."],["dc.date.accessioned","2018-11-07T11:12:37Z"],["dc.date.available","2018-11-07T11:12:37Z"],["dc.date.issued","2008"],["dc.description.abstract","Multidrug resistance (MDR) seriously limits the efficacy of chemotherapy in patients with cancer and leukemia. Active transport across membranes is essential for such cellular drug resistance, largely provided by ATP-binding cassette (ABC) transport proteins. Intracellular drug sequestration contributes to MDR; however, a genuine intracellular ABC transport protein with MDR function has not yet been identified. Analyzing the intrinsic drug efflux capacity of leukemic stem cells, we found the ABC transporter A3 (ABCA3) to be expressed consistently in acute myeloid leukemia (AML) samples. Greater expression of ABCA3 is associated with unfavorable treatment outcome, and in vitro, elevated expression induces resistance toward a broad spectrum of cytostatic agents. ABCA3 remains localized within the limiting membranes of lysosomes and multivesicular bodies, in which cytostatics are efficiently sequestered. In addition to AML, we also detected ABCA3 in a panel of lymphohematopoietic tissues and transformed cell lines. In conclusion, we identified subcellular drug sequestration mediated by the genuinely intracellular ABCA3 as being a clinically relevant mechanism of intrinsic MDR."],["dc.identifier.doi","10.1038/leu.2008.103"],["dc.identifier.isi","000258413400013"],["dc.identifier.pmid","18463677"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6063"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53706"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","0887-6924"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Intracellular ABC transporter A3 confers multidrug resistance in leukemia cells by lysosomal drug sequestration"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","143"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Molecular Cell Biology"],["dc.bibliographiccitation.lastpage","153"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Scharf, Christian"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Dyck, Lydia"],["dc.contributor.author","Rost, Ulrike"],["dc.contributor.author","Wenzel, Dirk"],["dc.contributor.author","Dhople, Vishnu M."],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Klemm, Florian"],["dc.date.accessioned","2018-11-07T09:58:48Z"],["dc.date.available","2018-11-07T09:58:48Z"],["dc.date.issued","2015"],["dc.description.abstract","Tumor cells secrete not only a variety of soluble factors, but also extracellular vesicles that are known to support the establishment of a favorable tumor niche by influencing the surrounding stroma cells. Here we show that tumor-derived microvesicles (T-MV) also directly influence the tumor cells by enhancing their invasion in a both autologousand heterologous manner. Neither the respective vesicle-free supernatant nor MV from benign mammary cells mediate invasion. Uptake of T-MV is essential for the proinvasive effect. We further identify the highly glycosylated form of the extracellular matrix metalloproteinase inducer (EMMPRIN) as a marker for proinvasive MV. EMMPRIN is also present at high levels on MV from metastatic breast cancer patients in vivo. Anti-EMMPRIN strategies, such as MV deglycosylation, gene knockdown, and specific blocking peptides, inhibit MV-induced invasion. Interestingly, the effect of EMMPRIN-bearing MV is not mediated by matrix metalloproteinases but by activation of the p38/MAPK signaling pathway in the tumor cells. In conclusion, T-MV stimulate cancer cell invasion via a direct feedback mechanism dependent on highly glycosylated EMMPRIN."],["dc.description.sponsorship","Deutsche Krebshilfe [109615]; DFG [BI 703/3-2]; eBIO MetastaSys (BMBF)"],["dc.identifier.doi","10.1093/jmcb/mju047"],["dc.identifier.isi","000355232100006"],["dc.identifier.pmid","25503107"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13819"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37445"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1759-4685"],["dc.relation.issn","1674-2788"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Tumor-derived microvesicles mediate human breast cancer invasion through differentially glycosylated EMMPRIN"],["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"]]

[["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"]]

[["dc.bibliographiccitation.firstpage","263"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Histochemistry and Cell Biology"],["dc.bibliographiccitation.lastpage","280"],["dc.bibliographiccitation.volume","132"],["dc.contributor.author","Majoul, Irina V."],["dc.contributor.author","Onichtchouk, Daria"],["dc.contributor.author","Butkevich, Eugenia"],["dc.contributor.author","Wenzel, Dirk"],["dc.contributor.author","Chailakhyan, Levon M."],["dc.contributor.author","Duden, Rainer"],["dc.date.accessioned","2018-11-07T11:24:53Z"],["dc.date.available","2018-11-07T11:24:53Z"],["dc.date.issued","2009"],["dc.description.abstract","Connexins are four-transmembrane-domain proteins expressed in all vertebrates which form permeable gap junction channels that connect cells. Here, we analysed Connexin-43 (Cx43) transport to the plasma membrane and studied the effects of small GTPases acting along the secretory pathway. We show that both GTP- and GDP-restricted Sar1 prevents exit of Cx43 from the endoplasmic reticulum (ER), but only GTP-restricted Sar1 arrests Cx43 in COP II-coated ER exit sites and accumulates 14-3-3 proteins in the ER fraction. FRET-FLIM data confirm that already in ER exit sites Cx43 exists in oligomeric form, suggesting an in vivo role for 14-3-3 in Cx43 oligomerization. Exit of Cx43 from the ER can be blocked by other factors-such as expression of the beta subunit of the COP I coat or p50/dynamitin that acts on the microtubule-based dynein motor complex. GTP-restricted Arf1 blocks Cx43 in the Golgi. Lastly, we show that GTP-restricted Arf6 removes Cx43 gap junction plaques from the cell-cell interface and targets them to degradation. These data provide a molecular explanation of how small GTPases act to regulate Cx43 transport through the secretory pathway, facilitating or abolishing cell-cell communication through gap junctions."],["dc.description.sponsorship","Wellcome Trust [047578]; Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.1007/s00418-009-0617-x"],["dc.identifier.isi","000269151300003"],["dc.identifier.pmid","19626334"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11202"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56511"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0948-6143"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Limiting transport steps and novel interactions of Connexin-43 along the secretory 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"]]

[["dc.bibliographiccitation.firstpage","2057"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","2066"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Gross, Julia Christina"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Wenzel, Dirk"],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2019-07-10T08:11:46Z"],["dc.date.available","2019-07-10T08:11:46Z"],["dc.date.issued","2013-11-01"],["dc.description.abstract","Recently, we have shown that macrophage (MΦ)-induced invasion of breast cancer cells requires upregulation of Wnt 5a in MΦ leading to activation of β-Catenin-independent Wnt signaling in the tumor cells. However, it remained unclear, how malignant cells induce Wnt 5a in MΦ and how it is transferred back to the cancer cells. Here we identify two types of extracellular particles as essential for this intercellular interaction in both directions. Plasma membrane-derived microvesicles (MV) as well as exosomes from breast cancer cells, although biologically distinct populations, both induce Wnt 5a in MΦ. In contrast, the particle-free supernatant and vesicles from benign cells, such as platelets, have no such effect. Induction is antagonized by the Wnt inhibitor Dickkopf-1. Subsequently, Wnt 5a is shuttled via responding MΦ-MV and exosomes to the tumor cells enhancing their invasion. Wnt 5a export on both vesicle fractions depends at least partially on the cargo protein Evenness interrupted (Evi). Its knockdown leads to Wnt 5a depletion of both particle populations and reduced vesicle-mediated invasion. In conclusion, MV and exosomes are critical for MΦ-induced invasion of cancer cells since they are responsible for upregulation of MΦ-Wnt 5a as well as for its delivery to the recipient cells via a reciprocal loop. Although of different biogenesis, both populations share common features regarding function and Evi-dependent secretion of non-canonical Wnts."],["dc.identifier.fs","603831"],["dc.identifier.pmid","24185202"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10760"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60794"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 3.0"],["dc.rights.uri","http://creativecommons.org/licenses/by/3.0"],["dc.title","Induction and transport of Wnt 5a during macrophage-induced malignant invasion is mediated by two types of extracellular vesicles."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1528"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","HAEMATOLOGICA-THE HEMATOLOGY JOURNAL"],["dc.bibliographiccitation.lastpage","1536"],["dc.bibliographiccitation.volume","94"],["dc.contributor.author","Chapuy, Björn"],["dc.contributor.author","Panse, Melanie"],["dc.contributor.author","Radunski, Ulf"],["dc.contributor.author","Koch, Raphael"],["dc.contributor.author","Wenzel, Dirk"],["dc.contributor.author","lnagaki, Nobuya"],["dc.contributor.author","Haase, Detlef"],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Wulf, Gerald G."],["dc.date.accessioned","2018-11-07T11:22:41Z"],["dc.date.available","2018-11-07T11:22:41Z"],["dc.date.issued","2009"],["dc.description.abstract","Background Inhibition of BCR-ABL tyrosine kinase activity has evolved as a mainstay of therapy for patients with chronic myeloid leukemia. However, a fraction of leukemic cells persists under targeted therapy and can lead to disease progression on cessation of treatment. Design and Methods We analyzed bone marrow progenitor cells with the side population phenotype, and characterized the role of the intracellular ABC transporter A3 in imatinib detoxification. Results BCR-ABL-positive leukemic cells contribute to the side population cell compartment in untreated patients. Such leukemic side population cells, as well as CD34-positive progenitors from chronic myeloid leukemia samples, strongly express the intracellular ABCA3. Functionally, ABCA3 levels are critical for the susceptibility of chronic myeloid leukemia blast cell lines to specific BCR-A-BL inhibition by imatinib. The transporter is localized in the limiting membrane of lysosomes and multivesicular bodies, and intracellular [(14)C]-labeled imatinib accumulates in such organelles. The lysosomal storage capacity increases with ABCA3 expression, thus regulating imatinib sequestration. Conclusions The intracellular ABC transporter A3 is expressed in chronic myeloid leukemia progenitor cells and may contribute to intrinsic imatinib resistance by facilitating lysosomal sequestration in chronic myeloid leukemia cells."],["dc.identifier.doi","10.3324/haematol.2009.008631"],["dc.identifier.isi","000272165800009"],["dc.identifier.pmid","19880777"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5958"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56030"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","0390-6078"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","ABC transporter A3 facilitates lysosomal sequestration of imatinib and modulates susceptibility of chronic myeloid leukemia cell lines to this drug"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1244"],["dc.bibliographiccitation.issue","5867"],["dc.bibliographiccitation.journal","Science"],["dc.bibliographiccitation.lastpage","1247"],["dc.bibliographiccitation.volume","319"],["dc.contributor.author","Trajkovic, Katarina"],["dc.contributor.author","Hsu, Chieh"],["dc.contributor.author","Chiantia, Salvatore"],["dc.contributor.author","Rajendran, Lawrence"],["dc.contributor.author","Wenzel, Dirk"],["dc.contributor.author","Wieland, Felix"],["dc.contributor.author","Schwille, Petra"],["dc.contributor.author","Bruegger, Britta"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2018-11-07T11:18:11Z"],["dc.date.available","2018-11-07T11:18:11Z"],["dc.date.issued","2008"],["dc.description.abstract","Intraluminal vesicles of multivesicular endosomes are either sorted for cargo degradation into lysosomes or secreted as exosomes into the extracellular milieu. The mechanisms underlying the sorting of membrane into the different populations of intraluminal vesicles are unknown. Here, we find that cargo is segregated into distinct subdomains on the endosomal membrane and that the transfer of exosome- associated domains into the lumen of the endosome did not depend on the function of the ESCRT ( endosomal sorting complex required for transport) machinery, but required the sphingolipid ceramide. Purified exosomes were enriched in ceramide, and the release of exosomes was reduced after the inhibition of neutral sphingomyelinases. These results establish a pathway in intraendosomal membrane transport and exosome formation."],["dc.identifier.doi","10.1126/science.1153124"],["dc.identifier.isi","000253530600044"],["dc.identifier.pmid","18309083"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6086"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54980"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Advancement Science"],["dc.relation.issn","0036-8075"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Ceramide triggers budding of exosome vesicles into multivesicular Endosomes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]