CD99 Regulates the Transport of MHC Class I Molecules from the Golgi Complex to the Cell Surface

Sohn, Hyung Sun; Shin, Young Kee; Lee, Im Soon; Bae, Young Mee; Suh, Young Ho; Kim, Min Kyung; Kim, Tae Jin; Jung, Kyeong Cheon; Park, Weon Seo; Park, Chan-Sik; Chung, Doo Hyun; Ahn, Kwang Seog; Kim, In Sun; Ko, Young Hyeh; Bang, Yung Jue; Kim, Chul Woo; Park, Seong Hoe

doi:10.4049/jimmunol.166.2.787

Cited by 57 publications

(62 citation statements)

References 46 publications

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“…Evidence for Rac-dependent protein export comes from the studies showing that Rac1 activated by the Ewing's sarcoma Ag CD99/Mic2 is critical for MHC class I export in B cells. In CD99-deficient cells, MHC class I molecules are synthesized and assembled normally, but are trapped at the level of the post-Golgi (46). This export defect can be rescued by activated Rac1 (47).…”

Section: Discussionmentioning

confidence: 99%

Lipid Raft-Associated GTPase Signaling Controls Morphology and CD8+ T Cell Stimulatory Capacity of Human Dendritic Cells

Jaksits

Bauer

Kriehuber

et al. 2004

The Journal of Immunology

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Their eponymous morphology and unique ability to activate naive T cells are hallmark features of dendritic cells (DCs). Specific properties of the actin cytoskeleton may define both characteristics. In search for regulators that coordinate DC phenotype and function, we observed strongly increased expression of the actin-remodeling GTPases Cdc42 and Rac1 during DC development from human stem cells. Cdc42 and Rac1 are constitutively active in immature DCs, and their activity is further up-regulated by maturational stimuli such as LPS or CD40L. Activation of Rac1 is associated with its rapid recruitment into lipid rafts. Cdc42 is not recruited into rafts, but readily activated by raft-associated moieties. The functional interplay of rafts, GTPases, and cortical actin is further shown by GTPase activation and actin remodeling after pharmacological disruption of lipid rafts and by the loss of the actin-based DC morphology by transfection of dominant-negative Cdc42 and Rac1. Both Cdc42 and Rac1 also control the transport of essential immunostimulatory molecules to the DC surface. Transfection with dominant-negative GTPases led to reduced surface expression of MHC class I and CD86. Consecutively, DCs display a reduced stimulatory capacity for CD8+ T cells, whereas MHC class II-dependent stimulation of CD4+ T cells remains unperturbed. We conclude that Cdc42 and Rac1 signaling controls DC morphology and conditions DCs for efficient CD8+ T cell stimulation.

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Section: Discussionmentioning

confidence: 99%

Lipid Raft-Associated GTPase Signaling Controls Morphology and CD8+ T Cell Stimulatory Capacity of Human Dendritic Cells

Jaksits

Bauer

Kriehuber

et al. 2004

The Journal of Immunology

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“…Available functional data on CD99 derive from triggering CD99 by agonistic monoclonal antibodies. In hematopoietic cells, CD99 ligation has been implicated in induction of homotypic aggregation, cell adhesion, migration (Bernard et al, 1995;Hahn et al, 1997;Schenkel et al, 2002), upregulation of TCR expression , vesicular transport of MHC molecules (Sohn et al, 2001), and costimulation to induce a Th1-type cytokine production (Waclavicek et al, 1998). In immature thymocytes and ESFT cells, CD99 antibodies induce massive apoptosis (Bernard et al, 1997;Sohn et al, 1998) as well as caspase-independent cell death (Cerisano et al, 2004) and increase sensitivity to chemotherapeutic agents (Scotlandi et al, 2000).…”

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confidence: 99%

Suppression of KCMF1 by constitutive high CD99 expression is involved in the migratory ability of Ewing's sarcoma cells

et al. 2005

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High CD99 expression levels and rearrangements of the EWS gene with ETS transcription factor genes characterize the Ewing's sarcoma family of tumors (ESFT). CD99 is a cell surface glycoprotein whose engagement has been implicated in cell proliferation as well as upregulation and transport of several transmembrane proteins in hematopoietic cells. In ESFT, antibody ligation of CD99 induces fast homotypic cell aggregation and cell death although its functional role in these processes remains largely unknown. Here, using an RNAi approach, we studied for the first time the consequences of modulated CD99 expression in six different ESFT cell lines, representing the most frequent variant forms of EWS gene rearrangement. CD99 suppression resulted in growth inhibition and reduced migration of ESFT cells. Among genes whose expression changes in response to CD99 modulation, the potassium-channel modulatory factor KCMF1 was consistently upregulated. In a series of 22 primary ESFT, KCMF1 expression levels inversely correlated with CD99 abundancy. Cells forced to express ectopic KCMF1 showed a similar reduction in migratory ability as CD99 silenced ESFT cells. Our results suggest that in ESFT, high CD99 expression levels contribute to the malignant properties of ESFT by promoting growth and migration of tumor cells and identify KCMF1 as a potential metastasis suppressor gene downregulated by high constitutive CD99 expression in ESFT.

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“…Surface levels of several receptor proteins were shown to be closely related to the function of hCD99. For example, upon engagement with anti-hCD99 Ab, surface expression of MHC class I (MHC I) molecules was upregulated on human thymocytes but downregulated in the absence of hCD99 (11)(12)(13). Additionally, upon IFN-g treatment of Jurkat cells, hCD99 was shown to associate with and increase the trafficking of MHC I to the cell membrane (14).…”

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confidence: 99%

Interaction of CD99 with Its Paralog CD99L2 Positively Regulates CD99L2 Trafficking to Cell Surfaces

Nam

Lee

et al. 2013

The Journal of Immunology

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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.

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CD99 Regulates the Transport of MHC Class I Molecules from the Golgi Complex to the Cell Surface

Cited by 57 publications

References 46 publications

Lipid Raft-Associated GTPase Signaling Controls Morphology and CD8+ T Cell Stimulatory Capacity of Human Dendritic Cells

Lipid Raft-Associated GTPase Signaling Controls Morphology and CD8+ T Cell Stimulatory Capacity of Human Dendritic Cells

Suppression of KCMF1 by constitutive high CD99 expression is involved in the migratory ability of Ewing's sarcoma cells

Interaction of CD99 with Its Paralog CD99L2 Positively Regulates CD99L2 Trafficking to Cell Surfaces

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