TY  - JOUR
AU  - Mentrup, Torben
AU  - Cabrera-Cabrera, Florencia
AU  - Fluhrer, Regina
AU  - Schröder, Bernd
TI  - Physiological functions of SPP/SPPL intramembrane proteases
JO  - Cellular and molecular life sciences
VL  - 77
IS  - 15
SN  - 1420-682X
CY  - Cham (ZG)
PB  - Springer International Publishing AG
M1  - DZNE-2020-01139
SP  - 2959-2979
PY  - 2020
AB  - 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.
KW  - Amyloid Precursor Protein Secretases: metabolism
KW  - Animals
KW  - Aspartic Acid Endopeptidases: chemistry
KW  - Aspartic Acid Endopeptidases: metabolism
KW  - Humans
KW  - Membrane Proteins: metabolism
KW  - Protein Transport
KW  - Proteolysis
KW  - Signal Transduction
KW  - Substrate Specificity
LB  - PUB:(DE-HGF)16
C6  - pmid:32052089
C2  - pmc:PMC7366577
DO  - DOI:10.1007/s00018-020-03470-6
UR  - https://pub.dzne.de/record/151555
ER  -