Differential stability of tetraspanin/tetraspanin interactions: role of palmitoylation

Charrin, Stéphanie; Manié, Serge N.; Oualid, Michael; Billard, Martine; Boucheix, Claude; Rubinstein, Eric

doi:10.1016/s0014-5793(02)02522-x

Cited by 209 publications

(259 citation statements)

References 42 publications

(58 reference statements)

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“…Given their intrinsic propensity to assemble into tightly packed microdomains (19), saturated acyl chains may stabilize and control spatial orientation of proteins within the tetraspanin complexes. Indeed, recent reports (20,21) and our present study demonstrate that mutations of the palmitoylation sites in CD9 and CD151 affect the association of the tetraspanins with one another within TERM. Importantly, here we show for the first time that (i) palmitoylation of tetraspanins is crucial for the recruitment of the associated non-tetraspanin partners into TERM, and (ii) palmitoylation-dependent localization of the ␣ 3 ␤ 1 integrin in TERM selectively affects its signaling potential.…”

supporting

confidence: 61%

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Expression of the Palmitoylation-deficient CD151 Weakens the Association of α3β1 Integrin with the Tetraspanin-enriched Microdomains and Affects Integrin-dependent Signaling

Berditchevski

Odintsova

Sawada

et al. 2002

Journal of Biological Chemistry

190

233

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Transmembrane proteins of the tetraspanin superfamily are assembled in multimeric complexes on the cell surface. Spatial orientation of tetraspanins within these complexes may affect signaling functions of the associated transmembrane receptors (e.g. integrins, receptor-type tyrosine kinases). The structural determinants that control assembly of the tetraspanin complexes are unknown. We have found that various tetraspanins and the ␣ 3 integrin subunit are palmitoylated. The stability and molecular composition of the palmitoylated ␣ 3 ␤ 1 -tetraspanin complexes are not affected by adhesion. To assess the significance of palmitoylation in the function of the ␣ 3 ␤ 1 -tetraspanin complexes we mapped the sites of palmitoylation for CD151. Mutation of six cysteines, Cys 11 , Cys 15 , Cys 79 , Cys 80 , Cys 242 , and Cys 243 was necessary to completely abolish palmitoylation of CD151. The association of the palmitoylation-deficient mutant of CD151 (CD151Cys8) with CD81 and CD63 was markedly decreased, but the interaction of the ␣ 3 ␤ 1 -CD151Cys8 complex with phosphatidylinositol 4-kinase was not affected. Ectopic expression of CD151Cys8 in Rat-1 cells impaired the interactions of the endogenous CD63 and CD81 with the ␣ 3 ␤ 1 integrin. Although the expression of the palmitoylation-deficient CD151 does not change cell spreading on the extracellular matrix, the number of focal adhesions increased. Adhesion-induced phosphorylation of PKB/c-Akt is markedly increased in cells expressing a palmitoylation-deficient mutant, thereby providing direct evidence for the role of the tetraspanin microdomains in regulation of the integrin-dependent phosphatidylinositol 3-kinase signaling pathway. In contrast, activation of FAK and ERK1/2 were not affected by the expression of CD151Cys8. Our results demonstrate that palmitoylation of tetraspanins is critical not only for the organization of the integrin-tetraspanin microdomains but also has a specific role in modulation of adhesion-dependent signaling.

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supporting

confidence: 61%

“…Multiple palmitoylation sites were also identified in the tetraspanin CD9 (20). However, in contrast to CD151 corresponding cysteines within the second transmembrane domain of CD9 do not seem to function as acceptor sites for palmitic acid.…”

Section: Discussionmentioning

confidence: 95%

Expression of the Palmitoylation-deficient CD151 Weakens the Association of α3β1 Integrin with the Tetraspanin-enriched Microdomains and Affects Integrin-dependent Signaling

Berditchevski

Odintsova

Sawada

et al. 2002

Journal of Biological Chemistry

190

233

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“…SSPN oligomers exhibit a characteristic tetraspanin migration profile during sucrose gradient centrifugation. SSPN migrates to fractions 3 to 6, which represent the low-density sucrose fractions where tetraspanin webs accumulate [40]. Analysis of molecular mass markers on non-denaturing sucrose gradients reveals that proteins of 60-200 kDa migrate within fractions 3 to 6, which is consistent with the predicted mass of SSPN oligomers (Fig.…”

Section: Site-directed Mutagenesis Of Sspn Reveals Complexity In Sspnsupporting

confidence: 74%

Structural and functional analysis of the sarcoglycan–sarcospan subcomplex

Miller

Wang

Nassar

et al. 2007

Experimental Cell Research

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Sarcospan is a component of the dystrophin-glycoprotein complex that forms a tight subcomplex with the sarcoglycans. The sarcoglycan-sarcospan subcomplex functions to stabilize α-dystroglycan at the plasma membrane and perturbations of this subcomplex are associated with autosomal recessive limb-girdle muscular dystrophy. In order to characterize protein interactions within this subcomplex, we first demonstrate that sarcospan forms homo-oligomers within the membrane. Experiments with a panel of site-directed mutants reveal that proper structure of the large extracellular loop is an important determinant of oligo formation. Furthermore, the intracellular N-and C-termini contribute to stability of sarcospan-mediated webs. Point mutation of each cysteine residue reveals that Cys 162 and Cys 164 within the large extracellular loop form disulfide bridges, which are critical for proper sarcospan structure. The extracellular domain of sarcospan also forms the main binding site for the sarcoglycans. We propose a model whereby sarcospan forms homo-oligomers that cluster the components of the dystrophin-glycoprotein complex within the membrane.

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“…In the glycosynapse 3, tetraspanins associate with each other through their transmembrane domains and palmitoylation of tetraspanins is an important mediator of these interactions [22,28]. When palmitoylation sites of CD151 are mutated, CD151 no longer interacts with other tetraspanin members, including CD9 [29] and CD81 [30].…”

Section: Introductionmentioning

confidence: 99%

The role of membrane microdomains in transmembrane signaling through the epithelial glycoprotein Gp140/CDCP1

Alvares

Dunn

Brown

et al. 2008

Biochimica et Biophysica Acta (BBA) - General Subjects

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Cell adhesion to the extracellular matrix (ECM) via integrin adhesion receptors initiates signaling cascades leading to changes in cell behavior. While integrin clustering is necessary to initiate cell attachment to the matrix, additional membrane components are necessary to mediate the transmembrane signals and the cell adhesion response that alter downstream cell behavior. Many of these signaling components reside in glycosphingolipid-rich and cholesterol-rich membrane domains such as Tetraspanin Enriched Microdomains (TEMs)/Glycosynapse 3 and DetergentResistant Microdomains (DRMs), also known as lipid rafts. In the following article, we will review examples of how components in these membrane microdomains modulate integrin adhesion after initial attachment to the ECM. Additionally, we will present data on a novel adhesion-responsive transmembrane glycoprotein Gp140/CUB Domain Containing Protein 1, which clusters in epithelial cell-cell contacts. Gp140 can then be phosphorylated by Src Family Kinases at tyrosine 734 in response to outside-in signals-possibly through interactions involving the extracellular CUB domains. Data presented here suggests that outside-in signals through Gp140 in cell-cell contacts assemble membrane clusters that associate with membrane microdomains to recruit and activate SFKs. Active SFKs then mediate phosphorylation of Gp140, SFK and PKCδ with Gp140 acting as a transmembrane scaffold for these kinases. We propose that the clustering of Gp140 and signaling components in membrane microdomains in cell-cell contacts contributes to changes in cell behavior.

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Differential stability of tetraspanin/tetraspanin interactions: role of palmitoylation

Cited by 209 publications

References 42 publications

Expression of the Palmitoylation-deficient CD151 Weakens the Association of α3β1 Integrin with the Tetraspanin-enriched Microdomains and Affects Integrin-dependent Signaling

Expression of the Palmitoylation-deficient CD151 Weakens the Association of α3β1 Integrin with the Tetraspanin-enriched Microdomains and Affects Integrin-dependent Signaling

Structural and functional analysis of the sarcoglycan–sarcospan subcomplex

The role of membrane microdomains in transmembrane signaling through the epithelial glycoprotein Gp140/CDCP1

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