TY  - JOUR
AU  - Lichtenthaler, Stefan
AU  - Lemberg, Marius K
AU  - Fluhrer, Regina
TI  - Proteolytic ectodomain shedding of membrane proteins in mammals-hardware, concepts, and recent developments.
JO  - The EMBO journal
VL  - 37
IS  - 15
SN  - 0261-4189
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - DZNE-2020-06445
SP  - e99456
PY  - 2018
AB  - Proteolytic removal of membrane protein ectodomains (ectodomain shedding) is a post-translational modification that controls levels and function of hundreds of membrane proteins. The contributing proteases, referred to as sheddases, act as important molecular switches in processes ranging from signaling to cell adhesion. When deregulated, ectodomain shedding is linked to pathologies such as inflammation and Alzheimer's disease. While proteases of the 'a disintegrin and metalloprotease' (ADAM) and 'beta-site APP cleaving enzyme' (BACE) families are widely considered as sheddases, in recent years a much broader range of proteases, including intramembrane and soluble proteases, were shown to catalyze similar cleavage reactions. This review demonstrates that shedding is a fundamental process in cell biology and discusses the current understanding of sheddases and their substrates, molecular mechanisms and cellular localizations, as well as physiological functions of protein ectodomain shedding. Moreover, we provide an operational definition of shedding and highlight recent conceptual advances in the field. While new developments in proteomics facilitate substrate discovery, we expect that shedding is not a rare exception, but rather the rule for many membrane proteins, and that many more interesting shedding functions await discovery.
KW  - ADAM Proteins: metabolism
KW  - Amyloid Precursor Protein Secretases: metabolism
KW  - Animals
KW  - Aspartic Acid Endopeptidases: metabolism
KW  - Cell Membrane: metabolism
KW  - Humans
KW  - Membrane Proteins: metabolism
KW  - Protein Domains: physiology
KW  - Protein Processing, Post-Translational: physiology
KW  - Proteolysis
KW  - Signal Transduction
KW  - Membrane Proteins (NLM Chemicals)
KW  - Amyloid Precursor Protein Secretases (NLM Chemicals)
KW  - Aspartic Acid Endopeptidases (NLM Chemicals)
KW  - BACE1 protein, human (NLM Chemicals)
KW  - ADAM Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:29976761
C2  - pmc:PMC6068445
DO  - DOI:10.15252/embj.201899456
UR  - https://pub.dzne.de/record/140123
ER  -