{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:40:36Z","timestamp":1787244036794,"version":"build-2736575974"},"reference-count":79,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009578","name":"Mizutani Foundation for Glycoscience","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009578","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Phosphacan, a chondroitin sulfate proteoglycan, is a repulsive cue of cerebellar granule cells. This study aims to explore the molecular mechanism. The glycosylphosphatidylinositol\u2010anchored neural adhesion molecule TAG\u20101 is a binding partner of phosphacan, suggesting that the repulsive effect of phosphacan is possibly because of its interaction with TAG\u20101. The repulsive effect was greatly reduced on primary cerebellar granule cells of TAG\u20101\u2010deficient mice. Surface plasmon resonance analysis confirmed the direct interaction of TAG\u20101 with chondroitin sulfate C. On postnatal days 1, 4, 7, 11, 15, and 20 and in adulthood, phosphacan was present in the molecular layer and internal granular layer, but not in the external granular layer. In contrast, transient TAG\u20101 expression was observed exclusively within the premigratory zone of the external granular layer on postnatal days 1, 4, 7, and 11. Boyden chamber cell migration assay demonstrated that phosphacan exerted its repulsive effect on the spontaneous and brain\u2010derived neurotrophic factor (BDNF)\u2010induced migration of cerebellar granule cells. The BDNF\u2010induced migration was inhibited by MK\u20102206, an Akt inhibitor. The pre\u2010treatment with a raft\u2010disrupting agent, methyl\u2010\u03b2\u2010cyclodextrin, also inhibited the BDNF\u2010induced migration, suggesting that lipid rafts are involved in the migration of cerebellar granule cells. In primary cerebellar granule cells obtained on postnatal day 7 and cultured for 7\u2009days, the ganglioside GD3 and TAG\u20101 preferentially localized in the cell body, whereas the ganglioside GD1b and NB\u20103 localized in not only the cell body but also neurites. Pre\u2010treatment with the anti\u2010GD3 antibody R24, but not the anti\u2010GD1b antibody GGR12, inhibited the spontaneous and BDNF\u2010induced migration, and attenuated BDNF\u2010induced Akt activation. These findings suggest that phosphacan is responsible for the repulsion of TAG\u20101\u2010expressing cerebellar granule cells via GD3 rafts to attenuate BDNF\u2010induced migration signaling.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15709-fig-0009-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.15709","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T11:45:05Z","timestamp":1665661505000},"page":"375-390","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Phosphacan acts as a repulsive cue in 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