Journal Article (Review Article)

DZNE-2020-06445

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Proteolytic ectodomain shedding of membrane proteins in mammals-hardware, concepts, and recent developments.

Lichtenthaler, S. (First author)DZNE* ; Lemberg, M. K. ; Fluhrer, R.DZNE*

2018
Wiley Hoboken, NJ [u.a.]

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Please use a persistent id in citations: doi:10.15252/embj.201899456

Abstract: 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.

Keyword(s): ADAM Proteins: metabolism (MeSH) ; Amyloid Precursor Protein Secretases: metabolism (MeSH) ; Animals (MeSH) ; Aspartic Acid Endopeptidases: metabolism (MeSH) ; Cell Membrane: metabolism (MeSH) ; Humans (MeSH) ; Membrane Proteins: metabolism (MeSH) ; Protein Domains: physiology (MeSH) ; Protein Processing, Post-Translational: physiology (MeSH) ; Proteolysis (MeSH) ; Signal Transduction (MeSH) ; Membrane Proteins ; Amyloid Precursor Protein Secretases ; Aspartic Acid Endopeptidases ; BACE1 protein, human ; ADAM Proteins

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Contributing Institute(s):

1. Neuroproteomics (AG Lichtenthaler)
2. Signal Peptide Peptidases as Models for γ-Secretase (AG Fluhrer)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; SCOPUS ; Web of Science Core Collection

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