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Interestingly, several vertebrate transmembrane Sema classes are capable of producing functional soluble ectodomains. However, little is known of soluble Sema6 ectodomains in the nervous system. Herein, we show that the soluble Sema6A ectodomain, <jats:styled-content style=\"fixed-case\">sS<\/jats:styled-content>ema6A, exhibits natural and protein kinase C (<jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content>)\u2010induced release. We show that <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content> mediates Sema6A phosphorylation at specific sites and while this phosphorylation is not the primary mechanism regulating <jats:styled-content style=\"fixed-case\">sS<\/jats:styled-content>ema6A production, we found that the intracellular domain confers resistance to ectodomain release. Finally, <jats:styled-content style=\"fixed-case\">sS<\/jats:styled-content>ema6A is functional as it promotes the cohesion of zebrafish early eye field explants. This suggests that in addition to its canonical contact\u2010mediated functions, Sema6A may have regulated, long\u2010range, forward\u2010signaling capacity.<\/jats:p>","DOI":"10.1002\/1873-3468.13561","type":"journal-article","created":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T06:43:22Z","timestamp":1564987402000},"page":"3015-3028","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>PKC<\/scp> induces release of a functional ectodomain of the guidance cue semaphorin6A"],"prefix":"10.1002","volume":"593","author":[{"given":"Riley M.","family":"St. Clair","sequence":"first","affiliation":[{"name":"Department of Biology University of Vermont Burlington VT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"Dumas","sequence":"additional","affiliation":[{"name":"Department of Biology University of Vermont Burlington VT 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