Protein-Protein Interactions in the Tetraspanin Web

Levy, Shoshana; Shoham, Tsipi

doi:10.1152/physiol.00015.2005

Cited by 211 publications

(237 citation statements)

References 70 publications

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“…Therefore, CD81 shed from the placenta into the maternal circulation may mediate the dysfunction of maternal endothelial cells and drive the development of the maternal manifestations of sPE. To test this hypothesis, it may be important to understand the molecular mechanisms of placental original CD81 webs or tetraspaninenriched microdomains (36).…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of CD81 inhibits cytotrophoblast invasion and mediates maternal endothelial cell dysfunction in preeclampsia

Shen

Diao

Sun

et al. 2017

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

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Preeclampsia (PE) is initiated by abnormal placentation in the early stages of pregnancy, followed by systemic activation of endothelial cells of the maternal small arterioles in the late second or third trimester (TM) of pregnancy. During normal pregnancy, placental cytotrophoblasts (CTBs) invade the maternal uterine wall and spiral arteries, whereas this process is interrupted in PE. However, it is not known how the malformed placenta triggers maternal endothelial crisis and the associated manifestations. Here, we have focused on the association of CD81 with PE. CD81, a member of the tetraspanin superfamily, plays significant roles in cell growth, adhesion, and motility. The function of CD81 in human placentation and its association with pregnancy complications are currently unknown. In the present study, we have demonstrated that CD81 was preferentially expressed in normal first TM placentas and progressively downregulated with gestation advance. In patients with early-onset severe PE (sPE), CD81 expression was significantly up-regulated in syncytiotrophoblasts (STBs), CTBs and the cells in the villous core. In addition, high levels of CD81 were observed in the maternal sera of patients with sPE. Overexpressing CD81 in CTBs significantly decreased CTB invasion, and culturing primary human umbilical vein endothelial cells (HUVECs) in the presence of a high dose of exogenous CD81 resulted in interrupted angiogenesis and endothelial cell activation in vitro. Importantly, the phenotype of human PE was mimicked in the CD81-induced rat model.is characterized by a new onset of hypertension and proteinuria after 20 wk of gestation. Early-onset severe PE (sPE, ≤ 34 wk) is associated with a high incidence of eclampsia, cerebrovascular complications, and fetal growth restriction, which severely threaten maternal and fetal health (1). Although the etiology of PE remains elusive, this disease has two known stages: In stage I, inadequate cytotrophoblast (CTB) invasion early in the pregnancy causes abnormal placentation; in stage II, systemic endothelial cell activation and clinical manifestations occur in the second or third trimester (TM), which are associated with the release of molecules and factors from the shallowly implanted placenta (2, 3).CD81 is a widely expressed tetraspanin that provides a scaffold for signaling molecules and orchestrates interactions between membrane-associated proteins to initiate signaling cascades that regulate cell adhesion, migration, and invasion (4-7). CD81 is also a tumor suppressor that inhibits the migration and invasion of some malignant tumor cells (8, 9). In addition, an increasing number of studies have reported that CD81 is one of the main components of exosomes and can be released into maternal circulation or delivered to certain organs and tissues (10-12). Our previous study showed that CD81 is highly expressed in LPS-treated HTR-8/SV neo cells derived from human first TM extravillous trophoblast cells and induces trophoblast syncytialization (13); however, the role of CD81 in ...

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Section: Discussionmentioning

confidence: 99%

Up-regulation of CD81 inhibits cytotrophoblast invasion and mediates maternal endothelial cell dysfunction in preeclampsia

Shen

Diao

Sun

et al. 2017

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

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“…This is mainly due to the existence of the largest, conserved domain, known as the large extracellular loop (LEL). Members of the tetraspanin family from different organisms are structurally and functionally related [18,31]. Phylogenetic analysis indicated that TSP2 of E. multilocularis is phylogenetically related to TSP2 [15], Sm23 [20] and SJC23 [21,22] of Schistosoma, the protective antigens against schistosomiasis, while TSP5 is closely related to the T24 antigen of T. solium, a diagnostic antigen for cysticercosis [26].…”

Section: Discussionmentioning

confidence: 99%

“…cell fusion, and host-parasite interactions [18]. The host-parasite interactions are thought to be associated with immune evasion [19], which has resulted in the use of tetraspanins as vaccines interfering with the schistosome survival strategy [19][20][21][22].…”

mentioning

confidence: 99%

Evaluation of Echinococcus multilocularis tetraspanins as vaccine candidates against primary alveolar echinococcosis

Dang

Yagi

Oku

et al. 2009

Vaccine

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“…Tetraspanins are expressed in all human cell types, and most cells generally express multiple tetraspanins (Levy 2005). Tetraspanins may be expressed on both the cell surface and on granular membranes (Israels 2005).…”

Section: Tetraspanin Structurementioning

confidence: 99%

“…Generally, the extracellular domains-mainly EC2-interact with laterally associated proteins or soluble ligands, the cytosolic regions associate with cytoskeletal or signaling molecules, and the transmembrane domains interact with other proteins necessary for maintenance of the tetraspanin web (Levy 2005). Thus, the tetraspanin web acts as a molecular facilitator, organizing membrane proteins and coupling receptors to signaling pathways (Levy 2005). …”

Section: Tetraspanin Webmentioning

confidence: 99%

The Tetraspanin CD9 Localizes to Platelet-Platelet Contacts and Regulates Thrombus Stability

Hill¹

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Protein-Protein Interactions in the Tetraspanin Web

Cited by 211 publications

References 70 publications

Up-regulation of CD81 inhibits cytotrophoblast invasion and mediates maternal endothelial cell dysfunction in preeclampsia

Up-regulation of CD81 inhibits cytotrophoblast invasion and mediates maternal endothelial cell dysfunction in preeclampsia

Evaluation of Echinococcus multilocularis tetraspanins as vaccine candidates against primary alveolar echinococcosis

The Tetraspanin CD9 Localizes to Platelet-Platelet Contacts and Regulates Thrombus Stability

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