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@ARTICLE{Niemeyer:140604,
author = {Niemeyer, Johannes and Mentrup, Torben and Heidasch, Ronny
and Müller, Stephan A and Biswas, Uddipta and Meyer, Rieke
and Papadopoulou, Alkmini A and Dederer, Verena and
Haug-Kröper, Martina and Adamski, Vivian and
Lüllmann-Rauch, Renate and Bergmann, Martin and Mayerhofer,
Artur and Saftig, Paul and Wennemuth, Gunther and
Jessberger, Rolf and Fluhrer, Regina and Lichtenthaler,
Stefan F and Lemberg, Marius K and Schröder, Bernd},
title = {{T}he intramembrane protease {SPPL}2c promotes male germ
cell development by cleaving phospholamban.},
journal = {EMBO reports},
volume = {20},
number = {3},
issn = {1469-221X},
address = {Hoboken, NJ [u.a.]},
publisher = {Wiley},
reportid = {DZNE-2020-06926},
pages = {e46449},
year = {2019},
abstract = {Signal peptide peptidase (SPP) and the four homologous
SPP-like (SPPL) proteases constitute a family of
intramembrane aspartyl proteases with selectivity for type
II-oriented transmembrane segments. Here, we analyse the
physiological function of the orphan protease SPPL2c,
previously considered to represent a non-expressed
pseudogene. We demonstrate proteolytic activity of SPPL2c
towards selected tail-anchored proteins. Despite shared ER
localisation, SPPL2c and SPP exhibit distinct, though
partially overlapping substrate spectra and inhibitory
profiles, and are organised in different high molecular
weight complexes. Interestingly, SPPL2c is specifically
expressed in murine and human testis where it is primarily
localised in spermatids. In mice, SPPL2c deficiency leads to
a partial loss of elongated spermatids and reduced motility
of mature spermatozoa, but preserved fertility. However,
matings of male and female SPPL2c-/- mice exhibit reduced
litter sizes. Using proteomics we identify the
sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2)-regulating
protein phospholamban (PLN) as a physiological SPPL2c
substrate. Accumulation of PLN correlates with a decrease in
intracellular Ca2+ levels in elongated spermatids that
likely contribute to the compromised male germ cell
differentiation and function of SPPL2c-/- mice.},
keywords = {Amino Acid Sequence / Animals / Aspartic Acid
Endopeptidases: chemistry / Aspartic Acid Endopeptidases:
metabolism / Calcium: metabolism / Calcium-Binding Proteins:
metabolism / Cell Membrane: enzymology / Endoplasmic
Reticulum: metabolism / Female / Germ Cells: metabolism /
HEK293 Cells / HeLa Cells / Homeostasis / Humans / Male /
Membrane Proteins: chemistry / Membrane Proteins: metabolism
/ Mice / Organ Specificity / Spermatids: metabolism /
Substrate Specificity / Testis: enzymology},
cin = {AG Haass / AG Fluhrer / AG Lichtenthaler},
ddc = {570},
cid = {I:(DE-2719)1110007 / I:(DE-2719)1110000-2 /
I:(DE-2719)1110006},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30733280},
pmc = {pmc:PMC6399600},
doi = {10.15252/embr.201846449},
url = {https://pub.dzne.de/record/140604},
}