Can Molecular Motors Drive Distance Measurements in Injured Neurons 英文参考文献.docVIP

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Can Molecular Motors Drive Distance Measurements in Injured Neurons 英文参考文献.doc

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Can Molecular Motors Drive Distance Measurements in Injured Neurons 英文参考文献

CanMolecularMotorsDriveDistanceMeasurementsin InjuredNeurons? NaamanKam1,YitzhakPilpel2,MikeFainzilber1* 1DepartmentofBiologicalChemistry,WeizmannInstituteofScience,Rehovot,Israel,2DepartmentofMolecularGenetics,WeizmannInstituteofScience,Rehovot,Israel Abstract Injurytonerveaxonsinducesdiverseresponsesinneuronalcellbodies,someofwhichareinfluencedbythedistancefrom thesiteofinjury.Thissuggeststhatneuronshavethecapacitytoestimatethedistanceoftheinjurysitefromtheircell body. Recent work has shown that the molecular motor dynein transports importin-mediated retrograde signaling complexesfromaxonallesionsitestocellbodies,raisingthequestionwhetherdynein-basedmechanismsenableaxonal distanceestimationsininjuredneurons?Weusedcomputersimulationstoexaminemechanismsthatmayprovidenerve cellswithdynein-dependentdistanceassessmentcapabilities.Amultiple-signalsmodelwaspostulatedbasedonthetime delaybetweenthearrivaloftwoormoresignalsproducedatthesiteofinjury–arapidsignalcarriedbyactionpotentialsor similarmechanismsandslowersignalscarriedbydynein.Thetimedelaybetweenthearrivalsofthesetwotypesofsignals shouldreflectthedistancetraversed,andsimulationsofthismodelshowthatitcanindeedprovideabasisfordistance measurementsinthecontextofnerveinjuries.Theanalysesindicatethatthesuggestedmechanismcanallownervecellsto discriminate between distances differing by 10% or more of their total axon length, and suggest that dynein-based retrogradesignalinginneuronscanbeutilizedforthispurposeoverdifferentscalesofnervesandorganisms.Moreover, suchamechanismmightalsofunctioninsynapsetonucleussignalinginuninjuredneurons.Thiscouldpotentiallyallowa neuron to dynamically sense the relative lengths of its processes on an ongoing basis, enabling appropriate metabolic outputfromcellbodytoprocesses. Citation: Kam N, Pilpel Y, Fainzilber M (2009) Can Molecular Motors Drive Distance Measurements in Injured Neurons?. PLoS Comput Biol 5(8): e1000477. doi:10.1371/journal.pcbi.1000477 Editor:JorgStelling,ETHZurich,Switze