Proteolytic Processing of Neuregulin 1 Type III by Three Intramembrane-cleaving Proteases

Intramembrane cleaving proteases (I-CLiPs) as guardians of shuttling proteins

The concept of proteases cleaving their substrates within the hydrophobic core of their transmembrane domains is very well established. in the past 15 years, various intramembrane cleaving proteases (i-CliPs) and their respective substrates have been identified.1 Besides the involvement in specific signaling pathways, for instance regulation of cholesterol metabolism or Notch signaling,1 a prot...

Proteolytic processing of delta-like 1 by ADAM proteases.

Delta-like 1 (Dll1) is a mammalian ligand for Notch receptors. Interactions between Dll1 and Notch in trans activate the Notch pathway, whereas Dll1 binding to Notch in cis inhibits Notch signaling. Dll1 undergoes proteolytic processing in its extracellular domain by ADAM10. In this work we demonstrate that Dll1 represents a substrate for several other members of the ADAM family. In co-transfec...

Sheddases and intramembrane-cleaving proteases: RIPpers of the membrane. Symposium on regulated intramembrane proteolysis.

Neuregulin-1 Type III Determines the Ensheathment Fate of Axons

The signals that determine whether axons are ensheathed or myelinated by Schwann cells have long been elusive. We now report that threshold levels of neuregulin-1 (NRG1) type III on axons determine their ensheathment fate. Ensheathed axons express low levels whereas myelinated fibers express high levels of NRG1 type III. Sensory neurons from NRG1 type III deficient mice are poorly ensheathed an...

Intramembrane-cleaving aspartic proteases and disease: presenilins, signal peptide peptidase and their homologs.

Recent studies demonstrate that presenilins (PSs) and signal peptide peptidase (SPP) are members of a novel protease family of integral membrane proteins that may utilize a catalytic mechanism similar to classic aspartic proteases such as pepsin, renin and cathepsin D. The defining features of the PSs and SPP are their ability to cleave substrate polypeptides within a transmembrane region, the ...