TY - JOUR
T1 - Proteostasis and "redoxtasis" in the secretory pathway
T2 - Tales of tails from ERp44 and immunoglobulins
AU - Anelli, Tiziana
AU - Sannino, Sara
AU - Sitia, Roberto
PY - 2015/5/19
Y1 - 2015/5/19
N2 - In multicellular organisms, some cells are given the task of secreting huge quantities of proteins. To comply with their duty, they generally equip themselves with a highly developed endoplasmic reticulum (ER) and downstream organelles in the secretory pathway. These professional secretors face paramount proteostatic challenges in that they need to couple efficiency and fidelity in their secretory processes. On one hand, stringent quality control (QC) mechanisms operate from the ER onward to check the integrity of the secretome. On the other, the pressure to secrete can be overwhelming, as for instance on antibody-producing cells during infection. Maintaining homeostasis is particularly hard when the products to be released contain disulfide bonds, because oxidative folding entails production of reactive oxygen species. How are redox homeostasis ("redoxtasis") and proteostasis maintained despite the massive fluxes of cargo proteins traversing the pathway? Here we describe recent findings on how ERp44, a multifunctional chaperone of the secretory pathway, can modulate these processes integrating protein QC, redoxtasis, and calcium signaling.
AB - In multicellular organisms, some cells are given the task of secreting huge quantities of proteins. To comply with their duty, they generally equip themselves with a highly developed endoplasmic reticulum (ER) and downstream organelles in the secretory pathway. These professional secretors face paramount proteostatic challenges in that they need to couple efficiency and fidelity in their secretory processes. On one hand, stringent quality control (QC) mechanisms operate from the ER onward to check the integrity of the secretome. On the other, the pressure to secrete can be overwhelming, as for instance on antibody-producing cells during infection. Maintaining homeostasis is particularly hard when the products to be released contain disulfide bonds, because oxidative folding entails production of reactive oxygen species. How are redox homeostasis ("redoxtasis") and proteostasis maintained despite the massive fluxes of cargo proteins traversing the pathway? Here we describe recent findings on how ERp44, a multifunctional chaperone of the secretory pathway, can modulate these processes integrating protein QC, redoxtasis, and calcium signaling.
KW - Disulfide bonds
KW - Endoplasmic reticulum
KW - ERp44
KW - Free radicals
KW - IgM
KW - Protein quality control
KW - Protein secretion
KW - Redox control
UR - http://www.scopus.com/inward/record.url?scp=84929298636&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84929298636&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2015.02.020
DO - 10.1016/j.freeradbiomed.2015.02.020
M3 - Article
C2 - 25744412
AN - SCOPUS:84929298636
VL - 83
SP - 323
EP - 330
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
ER -