{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T08:53:16Z","timestamp":1783587196754,"version":"3.55.0"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T00:00:00Z","timestamp":1398124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:p>Diverse mutations in the gene encoding the copper transporter ATP7A lead to X\u2010linked recessive Menkes disease or occipital horn syndrome. Recently, two unique <jats:italic>ATP7A<\/jats:italic> missense mutations, T994I and P1386S, were shown to cause isolated adult\u2010onset distal motor neuropathy. These mutations induce subtle defects in ATP7A intracellular trafficking resulting in preferential accumulation at the plasma membrane compared to wild\u2010type ATP7A. Immunoprecipitation assays revealed abnormal interaction between ATP7A<jats:sup>T994I<\/jats:sup> and p97\/VCP, a protein mutated in two autosomal dominant forms of motor neuron disease. Small\u2010interfering RNA knockdown of valosin\u2010containing protein corrected ATP7A<jats:sup>T994I<\/jats:sup> mislocalization. For ATP7A<jats:sup>P1386S<\/jats:sup>, flow cytometry documented that nonpermeabilized fibroblasts bound a C\u2010terminal ATP7A antibody, suggesting unstable insertion of the eighth transmembrane segment due to a helix\u2010breaker effect of the amino acid substitution. This could sabotage interaction of ATP7A<jats:sup>P1386S<\/jats:sup> with adaptor protein complexes. These molecular events appear to selectively disturb normal motor neuron function and lead to neurologic illness that takes years and sometimes decades to develop.<\/jats:p>","DOI":"10.1111\/nyas.12427","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T15:38:43Z","timestamp":1398181123000},"page":"49-54","source":"Crossref","is-referenced-by-count":32,"title":["ATP7A trafficking and mechanisms underlying the distal motor neuropathy induced by mutations in ATP7A"],"prefix":"10.1111","volume":"1314","author":[{"given":"Ling","family":"Yi","sequence":"first","affiliation":[{"name":"Section on Translational Neuroscience Molecular Medicine Program Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Kaler","sequence":"additional","affiliation":[{"name":"Section on Translational Neuroscience Molecular Medicine Program Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2010.01.003"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.01.027"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1094-195"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0193-20"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2010.180"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10191"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00997.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1242\/jcs.112.11.1721","article-title":"Identification of a di\u2010leucine motif within the C terminus domain of the Menkes disease protein that mediates endocytosis from the plasma membrane","volume":"112","author":"Francis M.J.","year":"1999","journal-title":"J. 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