Show simple item record

dc.contributor.authorSeamster, Pamela
dc.date.accessioned2012-02-01T17:38:19Z
dc.date.available2013-12-31T11:00:07Z
dc.date.issued2012-02-01
dc.date.submittedDecember 2011
dc.identifier.urihttp://hdl.handle.net/1928/17453
dc.description.abstractTransport of membrane-­bound organelles is critical to neuronal cell function yet mechanisms hitching vesicles to transport machinery remain elusive. Here we test whether jun-­‐kinase interacting protein (JIP-­‐1), a peripheral membrane scaffolding protein that binds kinesin light chain, is sufficient to mediate cargo transport in axons and study its competition with amyloid precursor protein cytoplasmic domain (APP-­‐C) and negative charge, also known motor receptors. Fluorescent beads (100 nm diameter) exhibit sequence-­‐specific fast anterograde transport (0.46μm/s instantaneous velocity) in the squid giant axon when conjugated to a 14-­‐ amino acid synthetic peptide derived from the carboxyl terminus of JIP-­‐1. JIP-­‐1-­‐ beads have statistically significant faster velocities, longer run lengths, and fewer pauses of shorter durations than APP-­‐C or negatively charged beads by cumulative probability analyses of thousands of motile beads compared by a nonparametric K-­‐S test, with a P=0.004. In competition experiments negatively charged beads gradually cease moving when co-­‐injected with either APP-­‐C or JIP-­‐1 beads, which sustain 90% motility. Co-­‐injection of APP-­‐C and JIP-­‐1 beads decreases each bead's propensity to move initially. At later time points JIP-­‐1-­‐beads recover frequency without further decreasing APP-­‐C moves, suggesting JIP-­‐1 recruits motors from a cryptic pool not accessible to APP-­‐C. Soluble JIP-­‐1 peptide inhibits JIP-­‐1 beads, with smaller effects on APP-­‐C and negatively charged beads. Thus the hierarchy for recruitment of transport machinery is JIP>APP>negative charge. Organelle transport may in part be regulated through the numbers, types and affinities of motor receptors displayed on each organelle's cytoplasmic surface.en_US
dc.description.sponsorshipINCBN IGERT and the NIHen_US
dc.language.isoen_USen_US
dc.subjectAxonal Transport, JIP-1, APP-Cen_US
dc.subject.lcshAxonal transport.
dc.subject.lcshNeurons--Physiology.
dc.subject.lcshSquids--Nervous system.
dc.subject.lcshSquids--Physiology.
dc.subject.lcshKinesin.
dc.titleSpatiotemporal dynamics of transport in the squid giant axon : competition between cargo motor receptors, JIP-1, APP-C, and negative chargeen_US
dc.typeThesisen_US
dc.description.degreeBiomedical Sciencesen_US
dc.description.levelMastersen_US
dc.description.departmentUniversity of New Mexico. Biomedical Sciences Graduate Programen_US
dc.description.advisorBearer, Elaine
dc.description.committee-memberBearer, Elaine
dc.description.committee-memberKoch, Steve
dc.description.committee-memberLidke, Diane
dc.description.committee-memberShuttleworth, Bill
dc.description.committee-memberSteinberg, Stan
emb.embargo.terms2013-12-31
dc.data.json{ "@context": { "rdf": "http://www.w3.org/1999/02/22-rdf-syntax-ns#", "rdfs": "http://www.w3.org/2000/01/rdf-schema#", "xsd": "http://www.w3.org/2001/XMLSchema#" }, "@graph": [ { "@id": "http://54.191.234.158/entities/resource/Squids--Nervous_system.", "@type": "http://schema.org/Intangible" }, { "@id": "http://hdl.handle.net/1928/17453", "@type": "http://schema.org/CreativeWork", "http://purl.org/montana-state/library/associatedDepartment": { "@id": "http://54.191.234.158/entities/resource/University_of_New_Mexico.__Biomedical_Sciences_Graduate_Program" }, "http://purl.org/montana-state/library/degreeGrantedForCompletion": "Biomedical Sciences", "http://purl.org/montana-state/library/hasEtdCommitee": { "@id": "http://54.191.234.158/entities/resource/1928/17453" }, "http://schema.org/about": [ { "@id": "http://54.191.234.158/entities/resource/Axonal_transport." }, { "@id": "http://54.191.234.158/entities/resource/Kinesin" }, { "@id": "http://54.191.234.158/entities/resource/Squids--Nervous_system." }, { "@id": "http://54.191.234.158/entities/resource/Neurons--Physiology" }, { "@id": "http://54.191.234.158/entities/resource/Squids--Physiology." }, { "@id": "http://54.191.234.158/entities/resource/Axonal_Transport_JIP-1_APP-C" } ], "http://schema.org/author": { "@id": "http://54.191.234.158/entities/resource/Seamster_Pamela" }, "http://schema.org/dateCreated": "December 2011", "http://schema.org/datePublished": "2012-02-01", "http://schema.org/description": "Transport of membrane-\u00adbound organelles is critical to neuronal cell function yet mechanisms hitching vesicles to transport machinery remain elusive. Here we test whether jun-\u00ad\u2010kinase interacting protein (JIP-\u00ad\u20101), a peripheral membrane scaffolding protein that binds kinesin light chain, is sufficient to mediate cargo transport in axons and study its competition with amyloid precursor protein cytoplasmic domain (APP-\u00ad\u2010C) and negative charge, also known motor receptors. Fluorescent beads (100 nm diameter) exhibit sequence-\u00ad\u2010specific fast anterograde transport (0.46\u03bcm/s instantaneous velocity) in the squid giant axon when conjugated to a 14-\u00ad\u2010 amino acid synthetic peptide derived from the carboxyl terminus of JIP-\u00ad\u20101. JIP-\u00ad\u20101-\u00ad\u2010 beads have statistically significant faster velocities, longer run lengths, and fewer pauses of shorter durations than APP-\u00ad\u2010C or negatively charged beads by cumulative probability analyses of thousands of motile beads compared by a nonparametric K-\u00ad\u2010S test, with a P=0.004. In competition experiments negatively charged beads gradually cease moving when co-\u00ad\u2010injected with either APP-\u00ad\u2010C or JIP-\u00ad\u20101 beads, which sustain 90% motility. Co-\u00ad\u2010injection of APP-\u00ad\u2010C and JIP-\u00ad\u20101 beads decreases each bead's propensity to move initially. At later time points JIP-\u00ad\u20101-\u00ad\u2010beads recover frequency without further decreasing APP-\u00ad\u2010C moves, suggesting JIP-\u00ad\u20101 recruits motors from a cryptic pool not accessible to APP-\u00ad\u2010C. Soluble JIP-\u00ad\u20101 peptide inhibits JIP-\u00ad\u20101 beads, with smaller effects on APP-\u00ad\u2010C and negatively charged beads. Thus the hierarchy for recruitment of transport machinery is JIP>APP>negative charge. Organelle transport may in part be regulated through the numbers, types and affinities of motor receptors displayed on each organelle's cytoplasmic surface.", "http://schema.org/inLanguage": "en_US", "http://schema.org/isPartOf": { "@id": "http://hdl.handle.net/1928/6665" }, "http://schema.org/name": "Spatiotemporal dynamics of transport in the squid giant axon : competition between cargo motor receptors, JIP-1, APP-C, and negative charge" }, { "@id": "http://54.191.234.158/entities/resource/Kinesin", "@type": "http://schema.org/Intangible" }, { "@id": "http://54.191.234.158/entities/resource/Axonal_transport.", "@type": "http://schema.org/Intangible" }, { "@id": "http://54.191.234.158/entities/resource/Squids--Physiology.", "@type": "http://schema.org/Intangible" }, { "@id": "http://54.191.234.158/entities/resource/Axonal_Transport_JIP-1_APP-C", "@type": "http://schema.org/Intangible" }, { "@id": "http://54.191.234.158/entities/resource/Neurons--Physiology", "@type": "http://schema.org/Intangible" }, { "@id": "http://54.191.234.158/entities/resource/Seamster_Pamela", "@type": "http://schema.org/Person" }, { "@id": "http://hdl.handle.net/1928/6665", "@type": "http://schema.org/WebSite" } ]}


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record