title: Interaction of CD99 with its paralog CD99L2 positively regulates CD99L2 trafficking to cell surfaces.
abstract: Mouse CD99 and its paralog CD99-like 2 (CD99L2) are surface proteins implicated in cellular adhesion and migration. Although their distributions overlap in a wide variety of cells, their physical/functional relationship is currently unknown. In this study, we show the interaction between the two molecules and its consequence for membrane trafficking of mouse (m)CD99L2. The interaction was analyzed by bimolecular fluorescence complementation, immunoprecipitation, and fluorescence resonance energy transfer assays. When coexpressed, mCD99 formed heterodimers with mCD99L2, as well as homodimers, and the heterodimers were localized more efficiently at the plasma membrane than were the homodimers. Their interaction was cytoplasmic domain-dependent and enhanced mCD99L2 trafficking to the plasma membrane regardless of whether it was transiently overexpressed or endogenously expressed. Surface levels of endogenous mCD99L2 were markedly low on thymocytes, splenic leukocytes, and CTL lines derived from CD99-deficient mice. Importantly, the surface levels of mCD99L2 on mCD99-deficient cells recovered significantly when wild-type mCD99 was exogenously introduced, but they remained low when a cytoplasmic domain mutant of mCD99 was introduced. Our results demonstrate a novel role for mCD99 in membrane trafficking of mCD99L2, providing useful insights into controlling transendothelial migration of leukocytes.
authors.affiliation: Department of Biomedical Sciences, Graduate School of Seoul National University, Seoul 110-799, Korea;
authors.forename: Giri
authors.initials: G
authors.lastname: Nam
authors.forename: Young-Kwan
authors.initials: YK
authors.lastname: Lee
authors.forename: Hye Yeong
authors.initials: HY
authors.lastname: Lee
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Ma
authors.forename: Masatake
authors.initials: M
authors.lastname: Araki
authors.forename: Kimi
authors.initials: K
authors.lastname: Araki
authors.forename: Seungbok
authors.initials: S
authors.lastname: Lee
authors.forename: Im-Soon
authors.initials: IS
authors.lastname: Lee
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
mesh_terms: D000071443:12E7 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D019281:Dimerization; D020440:Gene Duplication; D005786:Gene Expression Regulation / Q000235:genetics; D007962:Leukocytes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021381:Protein Transport / Q000235:genetics; D057705:Transendothelial and Transepithelial Migration / Q000235:genetics / Q000276:immunology; D019076:Transgenes / Q000235:genetics
chemical_list: D000071443:12E7 Antigen; D015703:Antigens, CD; C522605:Cd99 protein, mouse