The Tetraspanin Tspan8 Associates with Endothelin Converting Enzyme ECE1 and Regulates Its Activity

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Zhu, Yingying | Saint-Pol, Julien | Nguyen, Viet | Rubinstein, Eric | Boucheix, Claude | Greco, Céline

Edité par CCSD ; MDPI -

International audience. Tetraspanins are cell surface proteins that induce the compartmentalization of molecules with receptor, signaling, or enzymatic properties in microdomains that could serve the integration of transmembrane signals. Several knockouts illustrate their biological functions such as infertility (CD9/CD81), lymphoma development (CD37), immunological deficiency (CD81), or renal insufficiency (CD151). The link between molecular interactions and organ defects remains often difficult to decipher, as is the relationship between the expression of some tetraspanins and the outcome of tumors. High expression of Tspan8 in tumors is associated with poor prognosis, which may be due to increased cell motility and angiogenesis. In a model of colorectal tumor, we explored Tspan8 interacting molecules by mass spectrometry and found that compared to CD9, Tspan8 specifically recruits the endothelin converting enzyme ECE1 to tetraspanin-enriched microdomains and positively modulates its enzymatic activity. Convergence of Tspan8 and endothelin axis in tumor biology offers a new area of research.

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