biostudies-literatureBillcliff PGMedical Research CouncilWellcome TrustBiotechnology and Biological Sciences Research Council1253-63https://www.ebi.ac.uk/biostudies/studies/S-EPMC3828773biostudies-literatureUnknown2(11)The integral membrane protein CD317/tetherin has been associated with a plethora of biological processes, including restriction of enveloped virus release, regulation of B cell growth, and organisation of membrane microdomains. CD317 possesses both a conventional transmembrane (TM) domain and a glycophosphatidylinositol (GPI) anchor. We confirm that the GPI anchor is essential for CD317 to associate with membrane microdomains, and that the TM domain of CD44 is unable to rescue proper microdomain association of a ΔGPI-CD317 construct. Additionally, we demonstrate that the cytosolic amino terminal region of CD317 can function as a 'microdomain-excluding' motif, when heterologously expressed as part of a reporter construct. Finally, we show that two recently described isoforms of CD317 do notBiology openThe cytosolic N-terminus of CD317/tetherin is a membrane microdomain exclusion motif.PMC3828773WT086783MAG9721484BB/G021031/1Gorleku OABanting GBillcliff PGChamberlain LHfalseThe cytosolic N-terminus of CD317/tetherin is a membrane microdomain exclusion motif.The integral membrane protein CD317/tetherin has been associated with a plethora of biological processes, including restriction of enveloped virus release, regulation of B cell growth, and organisation of membrane microdomains. CD317 possesses both a conventional transmembrane (TM) domain and a glycophosphatidylinositol (GPI) anchor. We confirm that the GPI anchor is essential for CD317 to associate with membrane microdomains, and that the TM domain of CD44 is unable to rescue proper microdomain association of a ΔGPI-CD317 construct. Additionally, we demonstrate that the cytosolic amino terminal region of CD317 can function as a 'microdomain-excluding' motif, when heterologously expressed as part of a reporter construct. Finally, we show that two recently described isoforms of CD317 do not2013-01-01T00:00:00Z20132025-04-05T14:23:21.318Z2019-03-27T03:08:37ZS-EPMC38287732424486310.1242/bio.20135793