Shedding of glycan-modifying enzymes by signal peptide peptidase-like 3 (SPPL3) regulates cellular N-glycosylation.
Protein N-glycosylation is involved in a variety of physiological and pathophysiological processes such as autoimmunity, tumour progression and metastasis. Signal peptide peptidase-like 3 (SPPL3) is an intramembrane-cleaving aspartyl protease of the GxGD type. Its physiological function, however, has remained enigmatic, since presently no physiological substrates have been identified. We demonstrate that SPPL3 alters the pattern of cellular N-glycosylation by triggering the proteolytic release of active site-containing ectodomains of glycosidases and glycosyltransferases such as N-acetylglucosaminyltransferase V, β-1,3 N-acetylglucosaminyltransferase 1 and β-1,4 galactosyltransferase 1. Cleavage of these enzymes leads to a reduction in their cellular activity. In line with that, reduced expression of SPPL3 results in a hyperglycosylation phenotype, whereas elevated SPPL3 expression causes hypoglycosylation. Thus, SPPL3 plays a central role in an evolutionary highly conserved post-translational process in eukaryotes.
['Voss|Matthias|M|', 'Künzel|Ulrike|U|', 'Higel|Fabian|F|', 'Kuhn|Peer-Hendrik|PH|', 'Colombo|Alessio|A|', 'Fukumori|Akio|A|', 'Haug-Kröper|Martina|M|', 'Klier|Bärbel|B|', 'Grammer|Gudula|G|', 'Seidl|Andreas|A|', 'Schröder|Bernd|B|', 'Obst|Reinhard|R|', 'Steiner|Harald|H|', 'Lichtenthaler|Stefan F|SF|', 'Haass|Christian|C|', 'Fluhrer|Regina|R|']
D016282:Aspartic Acid Endopeptidases D005786:Gene Expression Regulation D006026:Glycoside Hydrolases D006031:Glycosylation D016695:Glycosyltransferases D006801:Humans D011134:Polysaccharides D011499:Protein Processing, Post-Translational
glycosyltransferases GxGD aspartyl proteases protein glycosylation signal peptide peptidase like‐3