Journal Article

DZNE-2020-01139

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Physiological functions of SPP/SPPL intramembrane proteases

Mentrup, T. ; Cabrera-Cabrera, F. ; Fluhrer, R.DZNE* ; Schröder, B. (Corresponding author)

2020
Springer International Publishing AG Cham (ZG)

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Please use a persistent id in citations: doi:10.1007/s00018-020-03470-6

Abstract: Intramembrane proteolysis describes the cleavage of substrate proteins within their hydrophobic transmembrane segments. Several families of intramembrane proteases have been identified including the aspartyl proteases Signal peptide peptidase (SPP) and its homologues, the SPP-like (SPPL) proteases SPPL2a, SPPL2b, SPPL2c and SPPL3. As presenilin homologues, they employ a similar catalytic mechanism as the well-studied γ-secretase. However, SPP/SPPL proteases cleave transmembrane proteins with a type II topology. The characterisation of SPP/SPPL-deficient mouse models has highlighted a still growing spectrum of biological functions and also promoted the substrate discovery of these proteases. In this review, we will summarise the current hypotheses how phenotypes of these mouse models are linked to the molecular function of the enzymes. At the cellular level, SPP/SPPL-mediated cleavage events rather provide specific regulatory switches than unspecific bulk proteolysis. By this means, a plethora of different cell biological pathways is influenced including signal transduction, membrane trafficking and protein glycosylation.

Keyword(s): Amyloid Precursor Protein Secretases: metabolism (MeSH) ; Animals (MeSH) ; Aspartic Acid Endopeptidases: chemistry (MeSH) ; Aspartic Acid Endopeptidases: metabolism (MeSH) ; Humans (MeSH) ; Membrane Proteins: metabolism (MeSH) ; Protein Transport (MeSH) ; Proteolysis (MeSH) ; Signal Transduction (MeSH) ; Substrate Specificity (MeSH)

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Contributing Institute(s):

1. 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 2020

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Database coverage:
; ; ; BIOSIS Previews ; BIOSIS Reviews Reports And Meetings ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; SCOPUS ; Web of Science Core Collection

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