Feb 14, 2020

Physiological functions of SPP/SPPL intramembrane proteases

Cellular and Molecular Life Sciences : CMLS
Torben MentrupBernd Schröder


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.

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Mentioned in this Paper

Protein Glycosylation
Membrane Protein Traffic
Peptide Hydrolases
SPPL2b protein, human
Biochemical Pathway
Signal Peptide Peptidase Activity
Sphingosine 1-phosphate
SPP1 protein, human

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