A physical and functional link between cholesterol and tetraspanins

Charrin, Stéphanie; Manié, Serge N.; Thiele, Christoph; Billard, Martine; Gerlier, Denis; Boucheix, Claude; Rubinstein, Eric

doi:10.1002/eji.200323884

Cited by 204 publications

(218 citation statements)

References 58 publications

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“…This is a detergent that precipitates cholesterol and large tetraspanin complexes but in which smaller tetraspanin-partner interactions appear to remain soluble (38). Indeed, digitonin has previously proved useful in identifying tetraspanin-partner interactions (12).…”

Section: Journal Of Biological Chemistrymentioning

confidence: 99%

The TspanC8 Subgroup of Tetraspanins Interacts with A Disintegrin and Metalloprotease 10 (ADAM10) and Regulates Its Maturation and Cell Surface Expression

Haining

Yang

Bailey

et al. 2012

Journal of Biological Chemistry

142

201

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Background: ADAM10 is a transmembrane metalloprotease that regulates development, inflammation, cancer, and Alzheimer disease. Results: The TspanC8 subgroup of tetraspanin membrane proteins interacts with and promotes ADAM10 maturation and cell surface localization. Conclusion: This study defines the TspanC8 tetraspanins as essential regulators of ADAM10. Significance: Focusing on specific TspanC8-ADAM10 complexes may allow ADAM10 therapeutic targeting in a cell typeand/or substrate-specific manner.

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Section: Journal Of Biological Chemistrymentioning

confidence: 99%

The TspanC8 Subgroup of Tetraspanins Interacts with A Disintegrin and Metalloprotease 10 (ADAM10) and Regulates Its Maturation and Cell Surface Expression

Haining

Yang

Bailey

et al. 2012

Journal of Biological Chemistry

142

201

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“…Digitonin interacts with cholesterol and precipitates proteins such as CD9 and CD81 that are targeted to lipid rafts (18). Upon crosslinking, the BCR rapidly translocates into lipid rafts (19,20).…”

Section: Translocation Of Bcr Complex To a Cholesterol-rich Microdomainmentioning

confidence: 99%

Monovalent ligation of the B cell receptor induces receptor activation but fails to promote antigen presentation

Kim

Pan

Korbel

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

116

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We explored the role of antigen valency in B cell receptor (BCR) activation and rearrangement of intracellular MHC class II compartments as factors that contribute to the efficacy of antigen presentation. Using primary B cells that express a hen egg lysozyme (HEL)-specific BCR, we found that oligomeric HEL more efficiently promoted both BCR activation and internalization than did monovalent HEL, although monovalent HEL, unlike monovalent Fab fragments of anti-Ig, readily triggered the BCR. Nonetheless, oligovalent ligation positions the BCR in a membrane microdomain that is distinct from one engaged in the course of monovalent ligation, as judged by detergent extraction of the BCR. A ctivation of B cell receptors by specific antigen unleashes a cascade of downstream events which includes alteration of transcriptional programs that lead to cell proliferation and differentiation (1-3). B cells further use their B cell receptors (BCRs) to facilitate the capture of antigen, and in doing so, they improve antigen presentation via class II MHC molecules (4). The latter event is essential for B cells to receive help from antigen-specific CD4 ϩ T cells and to differentiate eventually into memory cells or plasma cells that secrete high-affinity antibody (5).Antigen-specific B cells present peptides derived from cognate antigens to CD4 ϩ T cells at concentrations far below those required for other B cells that lack an antigen-specific receptor (6). This highly efficient mode of antigen presentation is thought to be a consequence of the dual role of the BCR in the delivery of specific antigen to MHC class II-containing peptide-loading compartments and in signaling that leads to enhanced generation of immunogenic peptides (7,8).BCR-transduced signals promote efficient delivery of antigens through activation of Syk and B cell linker protein (BLNK) (9, 10). In addition, BCR-transduced signals induce physical and chemical remodeling of intracellular class II MHC-compartments (11). In the A20͞IIA1.6 mouse B lymphoma cell line, BCR activation by receptor cross-linking induced reorganization, fusion, and acidification of Lamp1-positive late endosomes where class II MHC molecules and invariant chain accumulate (12). In A20 B cells that express an anti-DNP IgM, BCR stimulation led to the transient intracellular accumulation of MHC molecules in newly formed multivesicular bodies, into which the peptide exchange catalyst H2-M was recruited (13).Although these studies were among the first to shed light on a role for BCR signaling in MHC class II-mediated antigen presentation, virtually all of the studies that describe behavior of MHC class II molecules in relationship to the activation of B cells have been performed in transformed cell lines. Moreover, stimulation of the BCR is usually accomplished either by cross-linking receptors with anti-Ig antibodies or by transfecting established cell lines to express BCRs of known specificity to enable their ligation in an antigen-specific manner, which then still involves extensive crosslinking...

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“…There are controversial data in the literature about the role of cholesterol in the assembly of TERMs [7,36]. To compare effects of ganglioside and cholesterol depletion on the distribution of CD82-associated proteins we incubated HB2/CD82 cells with 20 mM MβCD for 1 h. Typically, after this treatment we removed approx.…”

Section: Figure 6 Exogenous Administration Of Gangliosides Does Not Amentioning

confidence: 99%

Gangliosides play an important role in the organization of CD82-enriched microdomains

Odintsova

Butters

Monti

et al. 2006

Biochemical Journal

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Four-transmembrane-domain proteins of the tetraspanin superfamily are the organizers of specific microdomains at the membrane [TERMs (tetraspanin-enriched microdomains)] that incorporate various transmembrane receptors and modulate their activities. The structural aspects of the organization of TERM are poorly understood. In the present study, we investigated the role of gangliosides in the assembly and stability of TERM. We demonstrated that inhibition of the glycosphingolipid biosynthetic pathway with specific inhibitors of glucosylceramide synthase [NB-DGJ (N-butyldeoxygalactonojirimycin) and PPMP (D-threo-1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol · HCl)] resulted in specific weakening of the interactions involving tetraspanin CD82. Furthermore, ectopic expression of the plasmamembrane-bound sialidase Neu3 in mammary epithelial cells also affected stability of the complexes containing CD82: its association with tetraspanin CD151 was decreased, but the association with EGFR [EGF (epidermal growth factor) receptor] was enhanced. The destabilization of the CD82-containing complexes upon ganglioside depletion correlated with the re-distribution of the proteins within plasma membrane. Importantly, depletion of gangliosides affected EGF-induced signalling only in the presence of CD82. Taken together, our results provide strong evidence that gangliosides play an important role in supporting the integrity of CD82-enriched microdomains. Furthermore, these results demonstrate that the association between different tetraspanins in TERM is controlled by distinct mechanisms and identify Neu3 as a first physiological regulator of the integrity of these microdomains.

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A physical and functional link between cholesterol and tetraspanins

Cited by 204 publications

References 58 publications

The TspanC8 Subgroup of Tetraspanins Interacts with A Disintegrin and Metalloprotease 10 (ADAM10) and Regulates Its Maturation and Cell Surface Expression

The TspanC8 Subgroup of Tetraspanins Interacts with A Disintegrin and Metalloprotease 10 (ADAM10) and Regulates Its Maturation and Cell Surface Expression

Monovalent ligation of the B cell receptor induces receptor activation but fails to promote antigen presentation

Gangliosides play an important role in the organization of CD82-enriched microdomains

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