Structural Bases for Tetraspanin Functions

Seigneuret, Michel; Conjeaud, Hélène; Zhang, Hui-Tang; Kong, Xiang‐Peng

doi:10.1007/978-94-007-6070-7_1

Cited by 7 publications

(6 citation statements)

References 69 publications

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“…2 A ); CD9 was chosen as a representative non-TspanC8 tetraspanin. These chimeras involved exchange of the entire LELs, or exchange of the so-called variable regions of the LEL that are relatively divergent in sequence, since these have been implicated in mediating interactions between other tetraspanins and their partners ( 27 ). These FLAG-tagged chimeric tetraspanins were then co-expressed with Myc-tagged human ADAM10 in HEK-293T cells.…”

Section: Resultsmentioning

confidence: 99%

TspanC8 Tetraspanins and A Disintegrin and Metalloprotease 10 (ADAM10) Interact via Their Extracellular Regions

Noy

Yang

Reyat

et al. 2016

Journal of Biological Chemistry

124

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A disintegrin and metalloprotease 10 (ADAM10) is a ubiquitously expressed transmembrane metalloprotease that cleaves the extracellular regions from its transmembrane substrates. ADAM10 is essential for embryonic development and is implicated in cancer, Alzheimer, and inflammatory diseases. The tetraspanins are a superfamily of 33 four-transmembrane proteins in mammals, of which the TspanC8 subgroup (Tspan5, 10, 14, 15, 17, and 33) promote ADAM10 intracellular trafficking and enzymatic maturation. However, the interaction between TspanC8s and ADAM10 has only been demonstrated in overexpression systems and the interaction mechanism remains undefined. To address these issues, an antibody was developed to Tspan14, which was used to show co-immunoprecipitation of Tspan14 with ADAM10 in primary human cells. Chimeric Tspan14 constructs demonstrated that the large extracellular loop of Tspan14 mediated its co-immunoprecipitation with ADAM10, and promoted ADAM10 maturation and trafficking to the cell surface. Chimeric ADAM10 constructs showed that membrane-proximal stalk, cysteine-rich, and disintegrin domains of ADAM10 mediated its co-immunoprecipitation with Tspan14 and other TspanC8s. This TspanC8-interacting region was required for ADAM10 exit from the endoplasmic reticulum. Truncated ADAM10 constructs revealed differential TspanC8 binding requirements for the stalk, cysteine-rich, and disintegrin domains. Moreover, Tspan15was the only TspanC8 to promote cleavage of the ADAM10 substrate N-cadherin, whereas Tspan14 was unique in reducing cleavage of the platelet collagen receptor GPVI. These findings suggest that ADAM10 may adopt distinct conformations in complex with different TspanC8s, which could impact on substrate selectivity. Furthermore, this study identifies regions of TspanC8s and ADAM10 for potential interaction-disrupting therapeutic targeting.

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Section: Resultsmentioning

confidence: 99%

TspanC8 Tetraspanins and A Disintegrin and Metalloprotease 10 (ADAM10) Interact via Their Extracellular Regions

Noy

Yang

Reyat

et al. 2016

Journal of Biological Chemistry

124

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“…Tetraspanins (TSPs) are a superfamily of plasma membrane-associated proteins consisting of four conserved transmembranes [ 58 ]. They have been used as vaccine candidates against schistosomiasis, echinococcosis and as diagnostic antigens for cysticercosis [ 2 , 20 , 59 , 60 ]; In addition, it was proven that tetraspanins in the tegument of schistosomula and adult worms can act as receptors for host ligands, including MHC molecules, allowing parasites to mask their non-self-status and escape host immune responses [ 61 ].…”

Section: Resultsmentioning

confidence: 99%

Analysis on Gene Expression Profile in Oncospheres and Early Stage Metacestodes from Echinococcus multilocularis

et al. 2016

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Alveolar echinococcosis is a worldwide zoonosis of great public health concern. Analysis of genome data for Echinococcus multilocularis has identified antigen families that can be used in diagnostic assays and vaccine development. However, little gene expression data is available for antigens of the egg and early larval stages. To address this information gap, we used a Next-Generation Sequencing approach to investigate three different stages (non-activated and activated oncospheres, and early stage metacestodes) of E. multilocularis (Nemuro strain). Transcriptome data analysis revealed that some diagnostic antigen gp50 isoforms and the antigen Eg95 family dominated in activated oncospheres, and the antigen B family dominated in early stage metacestodes. Furthermore, heat shock proteins and antigen II/3 are constantly expressed in the three stages. The expression pattern of various known antigens in E. multilocularis may give fundamental information for choosing candidate genes used in diagnosis and vaccine development.

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“…Kitadokoro et al reported the 3D structure of the large extracellular domain 2 (EC2) of CD81, and until recently, detailed structural analysis and molecular modelling have concentrated on this region [ 17 – 19 ]. These studies have shown that the EC2 can be delineated into two regions: a conserved domain consisting of three alpha helices, two of which form a ‘stalk’ adjoining TM3 and TM4, and a variable subdomain, forming part of the ‘head’ region.…”

Section: Tetraspanin Structurementioning

confidence: 99%

“…Molecular modelling suggested that the first small extracellular loop (13–30 aa) is likely to be shaded by the mushroom-shaped EC2 (70–130 aa). The distinctive variable regions are predicted to be responsible for protein-specific interactions [ 19 – 21 ]. The EC2 contains 4–8 cysteines, including a conserved CCG ‘signature’ motif, which forms at least two disulphide bridges that stabilise the head region.…”

Section: Tetraspanin Structurementioning

confidence: 99%

Tspan2: a tetraspanin protein involved in oligodendrogenesis and cancer metastasis

Yaseen

Monk

Partridge

2017

Biochemical Society Transactions

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Tetraspanin 2 (Tspan2) is one of the less well-characterised members of the tetraspanin superfamily, and its precise function in different human tissue types remains to be explored. Initial studies have highlighted its possible association in neuroinflammation and carcinogenesis. In the central nervous system, Tspan2 may contribute to the early stages of the oligodendrocyte differentiation into myelin-forming glia. Furthermore, in human lung cancer, Tspan2 could be involved in the progression of the tumour metastasis by modulating cancer cell motility and invasion functions. In this review, we discuss the available evidence for the potential role of Tspan2 and introduce possible strategies for disease targeting.

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Structural Bases for Tetraspanin Functions

Cited by 7 publications

References 69 publications

TspanC8 Tetraspanins and A Disintegrin and Metalloprotease 10 (ADAM10) Interact via Their Extracellular Regions

TspanC8 Tetraspanins and A Disintegrin and Metalloprotease 10 (ADAM10) Interact via Their Extracellular Regions

Analysis on Gene Expression Profile in Oncospheres and Early Stage Metacestodes from Echinococcus multilocularis

Tspan2: a tetraspanin protein involved in oligodendrogenesis and cancer metastasis

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