{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T18:31:09Z","timestamp":1772130669256,"version":"3.50.1"},"reference-count":119,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,11,13]],"date-time":"2014-11-13T00:00:00Z","timestamp":1415836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"C.D. Nelson Memorial Graduate Scholarship from Simon Fraser University"},{"name":"NSERC Postgraduate Scholarship"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioEssays"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:sec><jats:label\/><jats:p>Substantial evidence implicates fast axonal transport (FAT) defects in neurodegeneration. In Alzheimer's disease (AD), it is controversial whether transport defects cause or arise from amyloid\u2010\u03b2 (A\u03b2)\u2010induced toxicity. Using a novel, unbiased genetic screen, Morihara et al. identified kinesin light chain\u20101 splice variant E (KLC1vE) as a modifier of A\u03b2 accumulation. Here, we propose three mechanisms to explain this causal role. First, KLC1vE reduces APP transport, leading to A\u03b2 accumulation. Second, reduced transport of APP by KLC1vE triggers an ER stress response that activates the amyloidogenic pathway. Third, KLC1vE impairs transport of other KLC1 cargos that regulate amyloidogenesis, promoting A\u03b2 retention within the secretory pathway. Collectively, KLC1vE perpetuates a vicious cycle of A\u03b2 generation, kinase dysregulation, and global FAT impairment that inevitably leads to cellular toxicity. These concepts implicate alternative splicing of KLC1 in AD and suggest that the reciprocal influence of transport mechanisms on disease states contributes to neurodegeneration.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bies.201400131","type":"journal-article","created":{"date-parts":[[2014,11,13]],"date-time":"2014-11-13T12:11:06Z","timestamp":1415880666000},"page":"131-141","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["<i>Atlas stumbled<\/i>: Kinesin light chain\u20101 variant E triggers a vicious cycle of axonal transport disruption and amyloid\u2010\u03b2 generation in Alzheimer's disease"],"prefix":"10.1002","volume":"37","author":[{"given":"Kathlyn J.","family":"Gan","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Biochemistry Simon Fraser University Burnaby BC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Morihara","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Graduate School of Medicine Osaka University Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Silverman","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry Simon Fraser University Burnaby BC Canada"},{"name":"Department of Biological Sciences Simon Fraser University Burnaby BC Canada"},{"name":"Brain Research Centre University of British Columbia Vancouver BC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,11,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.17.030194.001411"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2056"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2013.08.007"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3380"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2014.05.002"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.04.013"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2012.03.006"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-6467-9_12"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4272-06.2007"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.12.007"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.293"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.11.1825"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-9-6"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/2047-9158-2-15"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0197-67"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2007.02.029"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.04.009"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.234674"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142637"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3463-09.2009"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2003.04.007"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21850"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0560-11.2011"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E12-12-0858"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-11-04499.2003"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn240"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds297"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-007-0707-8"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.132"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1105681"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1307345111"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200408113"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.09.039"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.111145398"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2014.03.015"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.115030"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00409a043"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-17-06374.2000"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90314-X"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005854107"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803575105"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1204824"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi049288l"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi981163r"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.8.4.675"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.141.2.443"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.152.5.959"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1234264"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0854.2003.00113.x"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.9.2.333"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601427"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.113.11.2047"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809576106"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01389"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03406"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.126.1.77"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/414643a"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00124-0"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200605099"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3089-04.2005"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.05.035"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201302078"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029755"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.138.3.671"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401652"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1159\/000332815"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200502043"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2558-08.2009"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2014.05.003"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010014\u20108695\u20108"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2008.10.005"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006312"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-2-14"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds109"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2009.00886.x"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.20121578"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806539200"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.08.077"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2168"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/925050"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.03.173"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0909142"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.04.014"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M803159200"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02018.x"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2692-08.2008"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22313"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4521-10.2010"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3028"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2011.08.003"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.10.9.15478"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.02.006"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2013.843670"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64516"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.06.035"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199702100-00012"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.67020699.x"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12037"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.3.281"},{"key":"e_1_2_9_101_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003792"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4883-04.2005"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.12.014"},{"key":"e_1_2_9_104_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57256"},{"key":"e_1_2_9_105_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2007.06.062"},{"key":"e_1_2_9_106_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087014"},{"key":"e_1_2_9_107_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901229106"},{"key":"e_1_2_9_108_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.20207"},{"key":"e_1_2_9_109_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0751085.x"},{"key":"e_1_2_9_110_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200301115"},{"key":"e_1_2_9_111_1","doi-asserted-by":"publisher","DOI":"10.1002\/cm.20488"},{"key":"e_1_2_9_112_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600237"},{"key":"e_1_2_9_113_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e06-05-0453"},{"key":"e_1_2_9_114_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033943"},{"key":"e_1_2_9_115_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.075168"},{"key":"e_1_2_9_116_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201001057"},{"key":"e_1_2_9_117_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200605097"},{"key":"e_1_2_9_118_1","doi-asserted-by":"publisher","DOI":"10.1515\/RNS.2011.048"},{"key":"e_1_2_9_119_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-012-9940-0"},{"key":"e_1_2_9_120_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)01912-7"}],"container-title":["BioEssays"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbies.201400131","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbies.201400131","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bies.201400131","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T18:33:17Z","timestamp":1696617197000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bies.201400131"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,13]]},"references-count":119,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,2]]}},"alternative-id":["10.1002\/bies.201400131"],"URL":"https:\/\/doi.org\/10.1002\/bies.201400131","archive":["Portico"],"relation":{},"ISSN":["0265-9247","1521-1878"],"issn-type":[{"value":"0265-9247","type":"print"},{"value":"1521-1878","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,13]]},"assertion":[{"value":"2014-11-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}