Klopfenstein, Dieter R.

[["dc.bibliographiccitation.firstpage","347"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cell"],["dc.bibliographiccitation.lastpage","358"],["dc.bibliographiccitation.volume","109"],["dc.contributor.author","Klopfenstein, Dieter R."],["dc.contributor.author","Tomishige, Michio"],["dc.contributor.author","Stuurman, Nico"],["dc.contributor.author","Vale, Ronald D."],["dc.date.accessioned","2020-11-03T15:23:55Z"],["dc.date.available","2020-11-03T15:23:55Z"],["dc.date.issued","2002"],["dc.identifier.doi","10.1016/S0092-8674(02)00708-0"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/68142"],["dc.relation.issn","0092-8674"],["dc.title","Role of Phosphatidylinositol(4,5)bisphosphate Organization in Membrane Transport by the Unc104 Kinesin Motor"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e1001200"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","PLoS Genetics"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Kumar, Jitendra"],["dc.contributor.author","Choudhary, Bikash C."],["dc.contributor.author","Metpally, Raghu"],["dc.contributor.author","Zheng, Qun"],["dc.contributor.author","Nonet, Michael L."],["dc.contributor.author","Ramanathan, Sowdhamini"],["dc.contributor.author","Klopfenstein, Dieter Robert"],["dc.contributor.author","Koushika, Sandhya P."],["dc.date.accessioned","2018-11-07T08:37:48Z"],["dc.date.available","2018-11-07T08:37:48Z"],["dc.date.issued","2010"],["dc.description.abstract","UNC-104/KIF1A is a Kinesin-3 motor that transports synaptic vesicles from the cell body towards the synapse by binding to PI(4,5)P(2) through its PH domain. The fate of the motor upon reaching the synapse is not known. We found that wild-type UNC-104 is degraded at synaptic regions through the ubiquitin pathway and is not retrogradely transported back to the cell body. As a possible means to regulate the motor, we tested the effect of cargo binding on UNC-104 levels. The unc-104(e1265) allele carries a point mutation (D1497N) in the PI(4,5)P2 binding pocket of the PH domain, resulting in greatly reduced preferential binding to PI(4,5)P2 in vitro and presence of very few motors on pre-synaptic vesicles in vivo. unc-104(e1265) animals have poor locomotion irrespective of in vivo PI(4,5) P2 levels due to reduced anterograde transport. Moreover, they show highly reduced levels of UNC-104 in vivo. To confirm that loss of cargo binding specificity reduces motor levels, we isolated two intragenic suppressors with compensatory mutations within the PH domain. These show partial restoration of in vitro preferential PI(4,5)P2 binding and presence of more motors on pre-synaptic vesicles in vivo. These animals show improved locomotion dependent on in vivo PI(4,5)P2 levels, increased anterograde transport, and partial restoration of UNC-104 protein levels in vivo. For further proof, we mutated a conserved residue in one suppressor background. The PH domain in this triple mutant lacked in vitro PI(4,5)P2 binding specificity, and the animals again showed locomotory defects and reduced motor levels. All allelic variants show increased UNC-104 levels upon blocking the ubiquitin pathway. These data show that inability to bind cargo can target motors for degradation. In view of the observed degradation of the motor in synaptic regions, this further suggests that UNC-104 may get degraded at synapses upon release of cargo."],["dc.identifier.doi","10.1371/journal.pgen.1001200"],["dc.identifier.isi","000284587100014"],["dc.identifier.pmid","21079789"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6893"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18626"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1553-7390"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","The Caenorhabditis elegans Kinesin-3 Motor UNC-104/KIF1A Is Degraded upon Loss of Specific Binding to Cargo"],["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","1031"],["dc.bibliographiccitation.issue","6187"],["dc.bibliographiccitation.journal","Science"],["dc.bibliographiccitation.lastpage","1035"],["dc.bibliographiccitation.volume","344"],["dc.contributor.author","Fakhri, Nikta"],["dc.contributor.author","Wessel, Alok D."],["dc.contributor.author","Willms, Charlotte"],["dc.contributor.author","Pasquali, Matteo"],["dc.contributor.author","Klopfenstein, Dieter R."],["dc.contributor.author","MacKintosh, Frederick C."],["dc.contributor.author","Schmidt, Christoph"],["dc.date.accessioned","2017-09-07T11:46:14Z"],["dc.date.available","2017-09-07T11:46:14Z"],["dc.date.issued","2014"],["dc.description.abstract","Cells are active systems with molecular force generation that drives complex dynamics at the supramolecular scale. We present a quantitative study of molecular motions in cells over times from milliseconds to hours. Noninvasive tracking was accomplished by imaging highly stable near-infrared luminescence of single-walled carbon nanotubes targeted to kinesin-1 motor proteins in COS-7 cells. We observed a regime of active random \"stirring\" that constitutes an intermediate mode of transport, different from both thermal diffusion and directed motor activity. High-frequency motion was found to be thermally driven. At times greater than 100 milliseconds, nonequilibrium dynamics dominated. In addition to directed transport along microtubules, we observed strong random dynamics driven by myosins that result in enhanced nonspecific transport. We present a quantitative model connecting molecular mechanisms to mesoscopic fluctuations."],["dc.identifier.doi","10.1126/science.1250170"],["dc.identifier.gro","3142119"],["dc.identifier.isi","000336495800046"],["dc.identifier.pmid","24876498"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4755"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1095-9203"],["dc.relation.issn","0036-8075"],["dc.title","High-resolution mapping of intracellular fluctuations using carbon nanotubes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3729"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Molecular Biology of the Cell"],["dc.bibliographiccitation.lastpage","3739"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Klopfenstein, Dieter R."],["dc.contributor.author","Vale, Ronald D"],["dc.date.accessioned","2020-11-03T15:23:33Z"],["dc.date.available","2020-11-03T15:23:33Z"],["dc.date.issued","2004-08"],["dc.description.abstract","UNC-104 (KIF1A) is a kinesin motor that transports synaptic vesicles from the neuronal cell body to the terminal. Previous in vitro studies have shown that a Dictyostelium relative of UNC-104 transports liposomes containing acidic phospholipids, but whether this interaction is needed for the recognition and transport of synaptic vesicles in metazoans remains unexplored. Here, we have introduced mutations in the nonmotor domain of UNC-104 and examined whether these mutant motors can rescue an unc-104 Caenorhabditis elegans strain. We show that a pleckstrin homology (PH) domain in UNC-104 is essential for membrane transport in living C. elegans, that this PH domain binds specifically to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)), and that point mutants in the PH domain that interfere with PI(4,5)P(2) binding in vitro also interfere with UNC-104 function in vivo. Several other lipid-binding modules could not effectively substitute for the UNC-104 PH domain in this in vivo assay. Real time imaging also revealed that a lipid-binding point mutation in the PH domain reduced movement velocity and processivity of individual UNC-104::GFP punctae in neurites. These results reveal a critical role for PI(4,5)P(2) binding in UNC-104-mediated axonal transport and shows that the cargo-binding properties of the distal PH domain can affect motor output."],["dc.identifier.doi","10.1091/mbc.e04-04-0326"],["dc.identifier.pmid","15155810"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/68138"],["dc.language.iso","en"],["dc.relation.issn","1059-1524"],["dc.title","The lipid binding pleckstrin homology domain in UNC-104 kinesin is necessary for synaptic vesicle transport in Caenorhabditis elegans"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5862"],["dc.bibliographiccitation.issue","15"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences of the United States of America"],["dc.bibliographiccitation.lastpage","5867"],["dc.bibliographiccitation.volume","109"],["dc.contributor.author","Chua, John Jia En"],["dc.contributor.author","Butkevich, Eugenia"],["dc.contributor.author","Worseck, Josephine M."],["dc.contributor.author","Kittelmann, Maike"],["dc.contributor.author","Gronborg, Mads"],["dc.contributor.author","Behrmann, Elmar"],["dc.contributor.author","Stelzl, Ulrich"],["dc.contributor.author","Pavlos, Nathan J."],["dc.contributor.author","Lalowski, Maciej M."],["dc.contributor.author","Eimer, Stefan"],["dc.contributor.author","Wanker, Erich E."],["dc.contributor.author","Klopfenstein, Dieter Robert"],["dc.contributor.author","Jahn, Reinhard"],["dc.date.accessioned","2018-11-07T09:11:12Z"],["dc.date.available","2018-11-07T09:11:12Z"],["dc.date.issued","2012"],["dc.description.abstract","Presynaptic nerve terminals are formed from preassembled vesicles that are delivered to the prospective synapse by kinesin-mediated axonal transport. However, precisely how the various cargoes are linked to the motor proteins remains unclear. Here, we report a transport complex linking syntaxin 1a (Stx) and Munc18, two proteins functioning in synaptic vesicle exocytosis at the presynaptic plasma membrane, to the motor protein Kinesin-1 via the kinesin adaptor FEZ1. Mutation of the FEZ1 ortholog UNC-76 in Caenorhabditis elegans causes defects in the axonal transport of Stx. We also show that binding of FEZ1 to Kinesin-1 and Munc18 is regulated by phosphorylation, with a conserved site (serine 58) being essential for binding. When expressed in C. elegans, wild-type but not phosphorylation-deficient FEZ1 (S58A) restored axonal transport of Stx. We conclude that FEZ1 operates as a kinesin adaptor for the transport of Stx, with cargo loading and unloading being regulated by protein kinases."],["dc.identifier.doi","10.1073/pnas.1113819109"],["dc.identifier.isi","000302533500062"],["dc.identifier.pmid","22451907"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26667"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","Phosphorylation-regulated axonal dependent transport of syntaxin 1 is mediated by a Kinesin-1 adapter"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","European Journal of Cell Biology"],["dc.bibliographiccitation.volume","85"],["dc.contributor.author","Wagner, Oliver"],["dc.contributor.author","Esposito, Alessandro"],["dc.contributor.author","Shen, K."],["dc.contributor.author","Wenzel, D."],["dc.contributor.author","Kohler, B."],["dc.contributor.author","Wouters, Fred S."],["dc.contributor.author","Klopfenstein, D. R."],["dc.date.accessioned","2018-11-07T10:11:06Z"],["dc.date.available","2018-11-07T10:11:06Z"],["dc.date.issued","2006"],["dc.format.extent","23"],["dc.identifier.isi","000237127500036"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39980"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Gmbh, Urban & Fischer Verlag"],["dc.publisher.place","Jena"],["dc.relation.conference","29th Annual Meeting of the German Society for Cell Biology"],["dc.relation.eventlocation","Braunschweig, GERMANY"],["dc.relation.issn","0171-9335"],["dc.title","How the LAR-interacting protein SYD-2 both clusters and regulates motor activity of KIF1A/UNC-104 in C. elegans"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","636"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Current Biology"],["dc.bibliographiccitation.lastpage","642"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Krahn, Michael P."],["dc.contributor.author","Klopfenstein, Dieter Robert"],["dc.contributor.author","Fischer, Nannette"],["dc.contributor.author","Wodarz, Andreas"],["dc.date.accessioned","2018-11-07T08:44:08Z"],["dc.date.available","2018-11-07T08:44:08Z"],["dc.date.issued","2010"],["dc.description.abstract","Cell polarity in higher animals is controlled by evolutionarily conserved protein complexes, which localize to the cytocortex in a polarized manner [1, 2]. The PAR-3/PAR-6/atypical protein kinase C (aPKC) complex is the first to become asymmetrically localized, and it controls the localization of additional complexes functioning further downstream in the regulation of cell polarity [3-9]. The first component of the PAR-3/PAR-6/aPKC complex that is localized to the cortex is Bazooka/PAR-3 (Baz), a large scaffolding protein [10]. In most cell types analyzed, loss of Baz function leads to loss of cell polarity [6, 8, 11]. Here we present a structure-function analysis of Baz focusing on its subcellular localization and function in four different polarized Drosophila cell types: the embryonic ectodermal epidermis, the follicular epithelium, embryonic neuroblasts, and the oocyte. We show that the PDZ domains of Baz are dispensable for its correct localization, whereas a conserved region in the C-terminal part of Baz to which no function had been assigned so far is required and sufficient for membrane localization. This region binds to phosphoinositide membrane lipids and thus mediates cortical localization of Baz by direct interaction with the plasma membrane. Our findings reveal a mechanism for the coupling of plasma membrane polarity and cortical polarity."],["dc.identifier.doi","10.1016/j.cub.2010.01.065"],["dc.identifier.isi","000276753100028"],["dc.identifier.pmid","20303268"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20129"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cell Press"],["dc.relation.issn","0960-9822"],["dc.title","Membrane Targeting of Bazooka/PAR-3 Is Mediated by Direct Binding to Phosphoinositide Lipids"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2263"],["dc.bibliographiccitation.issue","5590"],["dc.bibliographiccitation.journal","Science"],["dc.bibliographiccitation.lastpage","2267"],["dc.bibliographiccitation.volume","297"],["dc.contributor.author","Tomishige, Michio"],["dc.contributor.author","Klopfenstein, Dieter R."],["dc.contributor.author","Vale, Ronald D"],["dc.date.accessioned","2020-11-03T15:23:50Z"],["dc.date.available","2020-11-03T15:23:50Z"],["dc.date.issued","2002-09-27"],["dc.description.abstract","Unc104/KIF1A belongs to a class of monomeric kinesin motors that have been thought to possess an unusual motility mechanism. Unlike the unidirectional motion driven by the coordinated actions of the two heads in conventional kinesins, single-headed KIF1A was reported to undergo biased diffusional motion along microtubules. Here, we show that Unc104/KIF1A can dimerize and move unidirectionally and processively with rapid velocities characteristic of transport in living cells. These results suggest that Unc104/KIF1A operates in vivo by a mechanism similar to conventional kinesin and that regulation of motor dimerization may be used to control transport by this class of kinesins."],["dc.identifier.doi","10.1126/science.1073386"],["dc.identifier.pmid","12351789"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/68141"],["dc.language.iso","en"],["dc.relation.eissn","1095-9203"],["dc.relation.issn","0036-8075"],["dc.title","Conversion of Unc104/KIF1A kinesin into a processive motor after dimerization"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4942"],["dc.bibliographiccitation.issue","24"],["dc.bibliographiccitation.journal","EMBO Journal"],["dc.bibliographiccitation.lastpage","4954"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Gerson-Gurwitz, Adina"],["dc.contributor.author","Thiede, Christina"],["dc.contributor.author","Movshovich, Natalia"],["dc.contributor.author","Fridman, Vladimir"],["dc.contributor.author","Podolskaya, Maria"],["dc.contributor.author","Danieli, Tsafi"],["dc.contributor.author","Lakaemper, Stefan"],["dc.contributor.author","Klopfenstein, Dieter R."],["dc.contributor.author","Schmidt, Christoph"],["dc.contributor.author","Gheber, Larisa"],["dc.date.accessioned","2017-09-07T11:43:13Z"],["dc.date.available","2017-09-07T11:43:13Z"],["dc.date.issued","2011"],["dc.description.abstract","Kinesin-5 motors fulfil essential roles in mitotic spindle morphogenesis and dynamics as slow, processive microtubule (MT) plus-end directed motors. The Saccharomyces cerevisiae kinesin-5 Cin8 was found, surprisingly, to switch directionality. Here, we have examined directionality using single-molecule fluorescence motility assays and live-cell microscopy. On spindles, Cin8 motors mostly moved slowly (similar to 25 nm/s) towards the midzone, but occasionally also faster (similar to 55 nm/s) towards the spindle poles. In vitro, individual Cin8 motors could be switched by ionic conditions from rapid (380 nm/s) and processive minus-end to slow plus-end motion on single MTs. At high ionic strength, Cin8 motors rapidly alternated directionalities between antiparallel MTs, while driving steady plus-end relative sliding. Between parallel MTs, plus-end motion was only occasionally observed. Deletion of the uniquely large insert in loop 8 of Cin8 induced bias towards minus-end motility and affected the ionic strength-dependent directional switching of Cin8 in vitro. The deletion mutant cells exhibited reduced midzone-directed motility and efficiency to support spindle elongation, indicating the importance of directionality control for the anaphase function of Cin8. The EMBO Journal (2011) 30, 4942-4954. doi: 10.1038/emboj.2011.403; Published online 18 November 2011"],["dc.identifier.doi","10.1038/emboj.2011.403"],["dc.identifier.gro","3142614"],["dc.identifier.isi","000298368900012"],["dc.identifier.pmid","22101328"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0261-4189"],["dc.title","Directionality of individual kinesin-5 Cin8 motors is modulated by loop 8, ionic strength and microtubule geometry"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","16841"],["dc.bibliographiccitation.issue","27"],["dc.bibliographiccitation.journal","Journal of biological chemistry"],["dc.bibliographiccitation.lastpage","16850"],["dc.bibliographiccitation.volume","290"],["dc.contributor.author","Dueselder, Andre"],["dc.contributor.author","Fridman, Vladimir"],["dc.contributor.author","Thiede, Christina"],["dc.contributor.author","Wiesbaum, Alice"],["dc.contributor.author","Goldstein, Alina"],["dc.contributor.author","Klopfenstein, Dieter R."],["dc.contributor.author","Zaitseva, Olga"],["dc.contributor.author","Janson, Marcel E."],["dc.contributor.author","Gheber, Larisa"],["dc.contributor.author","Schmidt, Christoph"],["dc.date.accessioned","2017-09-07T11:43:42Z"],["dc.date.available","2017-09-07T11:43:42Z"],["dc.date.issued","2015"],["dc.description.abstract","The bipolar kinesin-5 motors are one of the major players that govern mitotic spindle dynamics. Their bipolar structure enables them to cross-link and slide apart antiparallel microtubules (MTs) emanating from the opposing spindle poles. The budding yeast kinesin-5 Cin8 was shown to switch from fast minus-end-to slow plus-end-directed motility upon binding between antiparallel MTs. This unexpected finding revealed a new dimension of cellular control of transport, the mechanism of which is unknown. Here we have examined the role of the C-terminal tail domain of Cin8 in regulating directionality. We first constructed a stable dimeric Cin8/kinesin-1 chimera (Cin8Kin), consisting of head and neck linker of Cin8 fused to the stalk of kinesin-1. As a single dimeric motor, Cin8Kin switched frequently between plus and minus directionality along single MTs, demonstrating that the Cin8 head domains are inherently bidirectional, but control over directionality was lost. We next examined the activity of a tetrameric Cin8 lacking only the tail domains (Cin8 Delta tail). In contrast to wild-type Cin8, the motility of single molecules of Cin8 Delta tail in high ionic strength was slow and bidirectional, with almost no directionality switches. Cin8 Delta tail showed only a weak ability to cross-link MTs in vitro. In vivo, Cin8 Delta tail exhibited bias toward the plus-end of the MTs and was unable to support viability of cells as the sole kinesin-5 motor. We conclude that the tail of Cin8 is not necessary for bidirectional processive motion, but is controlling the switch between plus-and minus-end-directed motility."],["dc.identifier.doi","10.1074/jbc.M114.620799"],["dc.identifier.gro","3141866"],["dc.identifier.isi","000357572800029"],["dc.identifier.pmid","25991727"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1945"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.eissn","1083-351X"],["dc.relation.issn","0021-9258"],["dc.title","Deletion of the Tail Domain of the Kinesin-5 Cin8 Affects Its Directionality"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]