|Dr. Matthias Voss|
|Unit for Cytokine and Metalloproteinase Research|
The junior group's primary research focus is the proteolytic cleavage of glycosyltransferases and other glycan-modifying enzymes in eukaryotic cells. Through their role in protein glycosylation, these enzymes are indispensable for synthesis and maturation of glycans decorating glycoproteins and -lipids. Even though their activity is foremost required in the Golgi network, it is well known that secretion of glycosyltransferases is a widespread phenomenon - but its physiological impact remained obscure. Given that most glycosyltransferases are single-pass membrane proteins, their ectodomains need to be separated from their membrane anchors by endoproteolysis prior to secretion. For many years, the protease(s) catalyzing this critical step for the ca. 200 Golgi enzymes have remained unknown. Early evidence suggested an involvement of BACE1 or furin(-like) protease(s), yet our more recent studies identified the intramembrane protease SPPL3 as major player in Golgi enzyme proteolysis and secretion (Voss et al. (2014), Kuhn*, Voss* et al. (2015)). Our research group's aims now are to systematically dissect cleavage and secretion of all ca. 200 Golgi-resident glycan-modifying enzymes. Specifically, we want to define precise substrate-protease pairs in the Golgi network under physiological conditions and aim to dissect in detail how Golgi enzyme proteolysis is organized and interlinked with Golgi homeostasis and organization. To do this, we employ a broad spectrum of biochemistry and molecular biology methodologies, ranging from CRISPR/Cas9 genome editing to proteomics.
In addition, in collaboration with my previous host lab at Karolinska Institutet and other institutions, a continuing interest lies in the cell biology and biochemistry of genes linked to primary immunodeficiencies and cancer predispositions. A notable example includes the twin tumour suppressors SAMD9 and SAMD9L, mutations in which have only recently emerged as cause of human hematologic malignancies and severe developmental defects.
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|Letzte Änderung / Last change: Mai 5, 2021|