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.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Niemeyer J,Mentrup T,Heidasch R,Müller SA,Biswas U,Meyer R,Papadopoulou AA,Dederer V,Haug-Kröper M,Adamski V,Lüllmann-Rauch R,Bergmann M,Mayerhofer A,Saftig P,Wennemuth G,Jessberger R,Fluhrer R,Lichtenthaler SF,Lemberdoi
10.15252/embr.201846449subject
Has Abstractpub_date
2019-03-01 00:00:00issue
3eissn
1469-221Xissn
1469-3178pii
embr.201846449journal_volume
20pub_type
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