{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:31:28Z","timestamp":1791070288172,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,1,31]],"date-time":"2008-01-31T00:00:00Z","timestamp":1201737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2008,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Schwannomas that occur spontaneously or in patients with neurofibromatosis Type 2, lack both alleles for the tumor suppressor and plasma membrane\u2010cytoskeleton linker merlin. We have shown that human primary schwannoma cells display activation of the RhoGTPases Rac1 and Cdc42 which results in highly dynamic and ongoing protrusive activity like ruffling. Ruffling is an initial and temporally limited step in the formation of intercellular contacts like adherens junctions that are based on the cadherin\u2010catenin system. We tested if there is a connection between Rac1\u2010induced ongoing ruffling and the maintenance, stabilization and functionality of adherens junctions and if this is of relevance in human, merlin\u2010deficient schwannoma cells. We show intense ongoing ruffling is not limited to membranes of single human primary schwannoma cells, but occurs also in membranes of contacting cells, even when confluent. Live cell imaging shows that newly formed contacts are released after a short time, suggesting disturbed formation or stabilization of adherens junctions. Morphology, high phospho\u2010tyrosine levels and cortactin staining indicate that adherens junctions are immature in human primary schwannoma cells, whereas they display characteristics of mature adherens junctions in human primary Schwann cells. When merlin is reintroduced, human primary schwannoma cells show only initial ruffling in contacting cells and adherens junctions appear more mature. We therefore propose that ongoing Rac\u2010induced ruffling causes immature adherens junctions and leads to impaired, nonfunctional intercellular adhesion in aggregation assays in merlin\u2010deficient schwannoma cells that could be an explanation for increased proliferation rates due to loss of contact inhibition or tumor development in general. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20629","type":"journal-article","created":{"date-parts":[[2008,1,31]],"date-time":"2008-01-31T23:16:53Z","timestamp":1201821413000},"page":"506-515","source":"Crossref","is-referenced-by-count":32,"title":["Impaired intercellular adhesion and immature adherens junctions in merlin\u2010deficient human primary schwannoma cells"],"prefix":"10.1002","volume":"56","author":[{"given":"C.","family":"Flaiz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Utermark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. B.","family":"Parkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Poetsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. O.","family":"Hanemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,1,31]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200610108"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.141.6.1449"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307234200"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1276"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.2.217"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200206043"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00216-2"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01385"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/nen.0b013e318093e555"},{"key":"e_1_2_6_11_1","first-page":"39","article-title":"Expression of E\u2010cadherin\u2010catenin complex in human benign schwannomas","volume":"17","author":"Hasegawa M","year":"2002","journal-title":"Histol Histopathol"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00130404-200401000-00006"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg146"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00382-4"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1054603"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.8.1121"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4865-05.2006"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200307132"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-21-08572.2001"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202141"},{"key":"e_1_2_6_21_1","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1242\/jcs.115.16.3331","article-title":"Invasive behaviour of glioblastoma cell lines is associated with altered organisation of the cadherin\u2010catenin adhesion system","volume":"115","author":"Perego C","year":"2002","journal-title":"J Cell Sci"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2006.10.010"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M414154200"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1998.0179"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.1.69"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(01)00009-0"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(01)81334-9"},{"key":"e_1_2_6_28_1","first-page":"5770","article-title":"Cadherin dysfunction in a human cancer cell line: Possible involvement of loss of alpha\u2010catenin expression in reduced cell\u2013cell adhesivness","volume":"52","author":"Shimoyama Y","year":"1992","journal-title":"Cancer Res"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.145.5.1009"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)31525-9"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2005.tb00095.x"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2003.tb00034.x"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.11.015"},{"key":"e_1_2_6_34_1","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1242\/jcs.115.9.1837","article-title":"Reactive oxygen species mediate Rac\u2010induced loss of cell\u2010cell adhesion in primary human endothelial cells","volume":"115","author":"van Wetering S","year":"2002","journal-title":"J Cell Sci"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-10-04066.2002"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.6.2384-2394.2005"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fglia.20629","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.20629","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T23:12:12Z","timestamp":1700003532000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.20629"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,31]]},"references-count":35,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2008,4]]}},"alternative-id":["10.1002\/glia.20629"],"URL":"https:\/\/doi.org\/10.1002\/glia.20629","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,1,31]]}}}