Publication Date:
2019
Description:
The orphan protease SPPL2c was considered to represent a non‐expressed pseudogene. Two studies in this issue now identify physiological substrates of SPPL2c, and show that it plays a role in vesicle trafficking, Ca2+ transport and spermatid development.
Intramembrane proteases reside within the subcellular compartments of cells to carry out a multiplicity of functions. One such family is the signal peptide peptidase (SPP) and signal peptide peptidase‐like (SPPL) family. The SPP/SPPL family comprises several homologs of aspartyl‐intramembrane proteases, and recent studies demonstrate distinct compartmentalization for each and a largely unknown cadre of substrates. Due to their hydrophobic nature, identification of substrates for intramembrane proteases can be an arduous task. In this issue of EMBO Reports, two studies identify physiological substrates of SPPL2c (1, 2). SPPL2c targets a variety of SNARE proteins, thereby playing a significant role in vesicular transport from the ER and in turn influencing the composition of the Golgi. Furthermore, trafficking defects observed in SPPL2c lacking cells lead to morphological changes in the spermatid cells of the testes, the only known site of protein expression. In these cells, phospholamban, a single‐pass transmembrane regulator of the Ca2+ transporter SERCA, was also identified as an SPPL2c substrate that impacts Ca2+ storage. This may explain the SPPL2c effect on germ cell development.
Print ISSN:
1469-221X
Electronic ISSN:
1469-3178
Topics:
Biology
,
Medicine
