title: Tetraspanin 8 is an interactor of the metalloprotease meprin β within tetraspanin-enriched microdomains.
abstract: Meprin β is a dimeric type I transmembrane protein and acts as an ectodomain sheddase at the cell surface. It has been shown that meprin β cleaves the amyloid precursor protein (APP), thereby releasing neurotoxic amyloid β peptides and implicating a role of meprin β in Alzheimer's disease. In order to identify non-proteolytic regulators of meprin β, we performed a split ubiquitin yeast two-hybrid screen using a small intestinal cDNA library. In this screen we identified tetraspanin 8 (TSPAN8) as interaction partner for meprin β. As several members of the tetraspanin family were described to interact with metalloproteases thereby affecting their localization and/or activity, we hypothesized similar functions of TSPAN8 in the regulation of meprin β. We employed cell biological methods to confirm direct binding of TSPAN8 to meprin β. Surprisingly, we did not observe an effect of TSPAN8 on the catalytic activity of meprin β nor on the specific cleavage of its substrate APP. However, both proteins were identified as present in tetraspanin-enriched microdomains. Therefore we hypothesize that TSPAN8 might be important for the orchestration of meprin β at the cell surface with impact on certain proteolytic processes that have to be further identified.
authors.forename: Frederike
authors.initials: F
authors.lastname: Schmidt
authors.forename: Miryam
authors.initials: M
authors.lastname: Müller
authors.forename: Johannes
authors.initials: J
authors.lastname: Prox
authors.forename: Philipp
authors.initials: P
authors.lastname: Arnold
authors.forename: Caroline
authors.initials: C
authors.lastname: Schönherr
authors.forename: Claudia
authors.initials: C
authors.lastname: Tredup
authors.forename: Petra
authors.initials: P
authors.lastname: Minder
authors.forename: Henriette
authors.initials: H
authors.lastname: Ebsen
authors.forename: Ottmar
authors.initials: O
authors.lastname: Janssen
authors.forename: Wim
authors.initials: W
authors.lastname: Annaert
authors.forename: Claus
authors.initials: C
authors.lastname: Pietrzik
authors.forename: Dirk
authors.initials: D
authors.lastname: Schmidt-Arras
authors.forename: Erwin E
authors.initials: EE
authors.lastname: Sterchi
authors.forename: Christoph
authors.initials: C
authors.lastname: Becker-Pauly
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D021381:Protein Transport; D013379:Substrate Specificity; D059470:Tetraspanins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: C065609:TSPAN8 protein, human; D059470:Tetraspanins; D008666:Metalloendopeptidases; C053833:meprin A