Signal Peptide-Peptidase-Like 2c (SPPL2c) impairs vesicular transport and cleavage of SNARE proteins

ABSTRACT: Members of the GxGD-type intramembrane aspartyl proteases have emerged as key players in fundamental cellular processes like B-cell development or protein glycosylation, but also in development of pathologies like Alzheimer's disease or hepatitis virus infections. However, one member of this protease family, signal peptide peptidase-like 2c (SPPL2c), remains orphan and its capability of proteolysis as well as its physiological function are still enigmatic. Here we demonstrate that SPPL2c is catalytically active and identify a variety of SPPL2c candidate substrates using proteomics. The majority of the SPPL2c candidate substrates cluster to the biological process of vesicular trafficking. Analysis of selected SNARE proteins reveals proteolytic processing by SPPL2c that impairs vesicular transport and causes retention of cargo proteins in the endoplasmic reticulum. As a consequence, the integrity of subcellular compartments, in particular the Golgi, is disturbed. Together with a strikingly high physiological SPPL2c expression in testis, our data suggest involvement of SPPL2c in acrosome formation during spermatogenesis.

SUBMITTER: Alkmini Papadopoulou 

PROVIDER: S-SCDT-EMBOR-2018-46451-T | biostudies-other |

REPOSITORIES: biostudies-other