Proteolytic cleavage of Golgi glycosyltransferases by SPPL3 and other proteases and its implications for cellular glycosylation

• Published in: Biochimica et biophysica acta. General subjects Vol. 1868; no. 10; p. 130668
• Main Author: Voss, Matthias
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2024
• Subjects: Animals; Aspartic Acid Endopeptidases - metabolism; BACE1; Extracellular glycosylation; Glycosylation; Glycosyltransferase secretion; Glycosyltransferases - metabolism; Golgi apparatus; Golgi Apparatus - metabolism; Golgi enzyme; Humans; Intramembrane proteolysis; Peptide Hydrolases - metabolism; Proteolysis; SPPL3; Glycosyltransferase secretion; APP; GPI; TCR; CTS; LCMV; SNA; SPPL3; ADAM; SPP; LacNAc; GTf; COG; GlcNAc; GSL; KO; M6P; TMD; Golgi enzyme; Intramembrane proteolysis; ER; Golgi apparatus; BACE1; PC; CAR; Extracellular glycosylation; GARP; TGN; NK
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2024.130668

Glycosylation of proteins and lipids is of fundamental importance in multicellular eukaryotes. The vast diversity of glycan structures observed is generated in the Golgi apparatus by the concerted activity of >100 distinct enzymes, which include glycosyltransferases and other glycan-modifying enzymes. Well-known for decades, the majority of these enzymes is released from the Golgi apparatus and subsequently secreted into the extracellular space following endoproteolytic cleavage, but the underlying molecular mechanisms and the physiological implications have remained unexplored. This review will summarize our current knowledge of Golgi enzyme proteolysis and secretion and will discuss its conceptual implications for the regulation of cellular glycosylation and the organization of the Golgi apparatus. A particular focus will lie on the intramembrane protease SPPL3, which recently emerged as key protease facilitating Golgi enzyme release and has since been shown to affect a multitude of glycosylation-dependent physiological processes. [Display omitted] •Golgi enzymes are frequently cleaved off their membrane anchor and secreted•enzyme cleavage affects cellular glycosylation but its regulation is not understood•BACE1, furin and the intramembrane protease SPPL3 are known to cleave Golgi enzymes•genetic screens further highlight the capacity of SPPL3 to regulate glycosylation•the regulation of SPPL3-mediated Golgi enzyme cleavage is not understood