Protein trafficking and maturation regulate intramembrane proteolysis

Intramembrane Proteolysis of Signal

SnapShot: Cartography of Intramembrane Proteolysis

Intramembrane proteases hydrolyze peptide bonds within the cell membrane as the decision-making step of various signaling pathways or during general proteostasis. Although initially thought to be rare, fourteen proteases from four superfamilies are now known to be distributed among nearly every membrane compartment of a human cell. Each protease is endowed with specific enzymatic properties tha...

Allosteric regulation of rhomboid intramembrane proteolysis.

Proteolysis within the lipid bilayer is poorly understood, in particular the regulation of substrate cleavage. Rhomboids are a family of ubiquitous intramembrane serine proteases that harbour a buried active site and are known to cleave transmembrane substrates with broad specificity. In vitro gel and Förster resonance energy transfer (FRET)-based kinetic assays were developed to analyse cleava...

Annotated Classic Stepwise Regulatory Intramembrane Proteolysis

We are pleased to present a series of Annotated Classics celebrating 40 years of exciting biology in the pages of Cell. This installment revisits “Sterol-Regulated Release of SREBP-2 from Cell Membranes Requires Two Sequential Cleavages, One within a Transmembrane Segment” from the Brown and Goldstein lab. Here, Matthew Freeman comments on the elucidation of regulated two-step proteolysis of th...

Sphingomyelin Synthases Regulate Protein Trafficking and Secretion

Sphingomyelin synthases (SMS1 and 2) represent a class of enzymes that transfer a phosphocholine moiety from phosphatidylcholine onto ceramide thus producing sphingomyelin and diacylglycerol (DAG). SMS1 localizes at the Golgi while SMS2 localizes both at the Golgi and the plasma membrane. Previous studies from our laboratory showed that modulation of SMS1 and, to a lesser extent, of SMS2 affect...