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المؤلفون: Moritz Ballin, Wolfram Griep, Mehul Patel, Martin Karl, Torben Mentrup, Jhon Rivera‐Monroy, Brian Foo, Blanche Schwappach, Bernd Schröder
المصدر: The FEBS Journal. 290:2320-2337
مصطلحات موضوعية: Cell Biology, Molecular Biology, Biochemistry
الوصف: Signal peptide peptidase (SPP) and SPP-like (SPPL) aspartyl intramembrane proteases are known to contribute to sequential processing of type II-oriented membrane proteins referred to as regulated intramembrane proteolysis. The ER-resident family members SPP and SPPL2c were shown to also cleave tail-anchored proteins, including selected SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins facilitating membrane fusion events. Here, we analysed whether the related SPPL2a and SPPL2b proteases, which localise to the endocytic or late secretory pathway, are also able to process SNARE proteins. Therefore, we screened 18 SNARE proteins for cleavage by SPPL2a and SPPL2b based on cellular co-expression assays, of which the proteins VAMP1, VAMP2, VAMP3 and VAMP4 were processed by SPPL2a/b demonstrating the capability of these two proteases to proteolyse tail-anchored proteins. Cleavage of the four SNARE proteins was scrutinised at the endogenous level upon SPPL2a/b inhibition in different cell lines as well as by analysing VAMP1-4 levels in tissues and primary cells of SPPL2a/b double-deficient (dKO) mice. Loss of SPPL2a/b activity resulted in an accumulation of VAMP1-4 in a cell type- and tissue-dependent manner, identifying these proteins as SPPL2a/b substrates validated in vivo. Therefore, we propose that SPPL2a/b control cellular levels of VAMP1-4 by initiating the degradation of these proteins, which might impact cellular trafficking.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::67b88ec206d212f07befe44e09ffa478Test
https://doi.org/10.1111/febs.16610Test -
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المؤلفون: null Moritz Ballin, null Wolfram Griep, null Mehul Patel, null Martin Karl, null Torben Mentrup, null Jhon Rivera‐Monroy, null Brian Foo, null Blanche Schwappach, null Bernd Schröder
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::de45aa02179c05902d1ea9a4f90a6f68Test
https://doi.org/10.1111/febs.16610/v2/response1Test -
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