Proteostasis and "redoxtasis" in the secretory pathway: Tales of tails from ERp44 and immunoglobulins.
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.
Divisions of Genetics and Cell Biology, IRCCS Ospedale San Raffaele and Università Vita-Salute San Raffaele, 20132 Milan, Italy.
Tiziana
T
Anelli
Divisions of Genetics and Cell Biology, IRCCS Ospedale San Raffaele and Università Vita-Salute San Raffaele, 20132 Milan, Italy.
Sara
S
Sannino
Divisions of Genetics and Cell Biology, IRCCS Ospedale San Raffaele and Università Vita-Salute San Raffaele, 20132 Milan, Italy. Electronic address: r.sitia@hsr.it.
Roberto
R
Sitia
D000595:Amino Acid Sequence; D000818:Animals; D004721:Endoplasmic Reticulum / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D017510:Protein Folding; D055571:Secretory Pathway; D017386:Sequence Homology, Amino Acid
C451899:ERP44 protein, human; C520556:ERp44 protein, mouse; D007136:Immunoglobulins; D008565:Membrane Proteins; D018832:Molecular Chaperones
Disulfide bonds; ERp44; Endoplasmic reticulum; Free radicals; IgM; Protein quality control; Protein secretion; Redox control