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Sheddases and intramembrane‐cleaving proteases: RIPpers of the membrane
Author(s) -
Lichtenthaler Stefan F,
Steiner Harald
Publication year - 2007
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400978
Subject(s) - extant taxon , library science , biology , computer science , evolutionary biology
The Ringberg Symposium on Regulated Intramembrane Proteolysis took place between 27 and 30 November 2006, at the Ringberg Castle, Rottach‐Egern, Germany, and was organized by C. Haass.![][1] At the end of November 2006, 60 scientists met at Ringberg Castle in the beautiful Bavarian countryside of Lake Tegernsee to present and discuss recent findings in the field of regulated intramembrane proteolysis (RIP). The meeting was funded by the Collaborative Research Centre ‘Molecular Mechanisms of Neurodegeneration’ (SFB 596) of the German Research Foundation (DFG) and was organized by the co‐ordinator of the SFB, Christian Haass. RIP is an important area of research of the SFB 596 because it has a crucial role in Alzheimer disease—the most common neurodegenerative disorder. The meeting was the first of its kind in this research field and, as all participants agreed, was long overdue. RIP occurs in all organisms studied so far and is a regulated proteolytic cleavage mechanism typically required for either signal transduction or the degradation of membrane proteins (Brown et al , 2000). Although much has been learned about RIP, the meeting made it clear that many questions remain.In many cases, RIP starts with an initial cleavage of a single‐span membrane protein substrate with type I or II orientation. This cleavage, which is referred to as ectodomain shedding, occurs within the ectodomain at a peptide bond close to the transmembrane domain (TMD), either constitutively or in response to a ligand. Shedding results in the release of the ectodomain into the extracellular milieu and the generation of a membrane‐bound stub, which then undergoes a second cleavage within its TMD, called intramembrane proteolysis. Members of the disintegrin and metalloprotease (ADAM) family, matrix metalloproteases and the aspartyl proteases β‐site APP‐cleaving enzymes 1 and 2 (BACE1 and BACE2) carry out the ectodomain‐shedding step in most cases that have … [1]: /embed/graphic-1.gif