Newly synthesized secretory proteins undergo scrupulous quality control (QC) to avoid release of folding or assembly intermediates. High fidelity of secretion depends on retention in, or retrieval into, the early secretory compartment (ESC), where immature cargoes can complete folding and assembly. One of the QC chaperones is ERp44 that is located into ERGIC-Cis Golgi compartment (chaperone isolated several years ago by T. Anelli). ERp44 is a multifunctional chaperone of the PDI family that participates in protein folding, redox homeostasis and Ca2+ signaling. In order to study ERp44 function and regulation we divided the project in two major aims: 1) Pathophysiology of ERp44 activity and regulation and 2) Identification of ERp44 partners or regulatory molecules.
Studying how ERp44 is able to do all its different functions and its binding to different client proteins, we’ll understand more about mechanisms that integrate protein transport and signaling in the early exocytic compartment. This will improve our knowledge on the pathogenesis possibly leading to novel therapeutic strategies, for Selective IgM deficiency, Multiple Sulphatase Deficiency, and other diseases caused by defective proteostasis.
A dynamic study of protein secretion and aggregation in the secretory pathway.
Mossuto MF, Sannino S, Mazza D, Fagioli C, Vitale M, Yoboue ED, Sitia R, Anelli T.
PLoS One. 2014 Oct 3;9(10):e108496. doi: 10.1371/journal.pone.0108496. eCollection 2014.
PMID:25279560
Progressive quality control of secretory proteins in the early secretory compartment by ERp44.
Sannino S, Anelli T, Cortini M, Masui S, Degano M, Fagioli C, Inaba K, Sitia R.
J Cell Sci. 2014 Oct 1;127(Pt 19):4260-9. doi: 10.1242/jcs.153239. Epub 2014 Aug 5.
PMID:25097228
A pH-Regulated Quality Control Cycle for Surveillance of Secretory Protein Assembly.
Vavassori S, Cortini M, Masui S, Sannino S, Anelli T, Caserta IR, Fagioli C, Mossuto MF, Fornili A, van Anken E, Degano M, Inaba K, Sitia R.
Mol Cell. 2013 May 14. doi:pii: S1097-2765(13)00297-9. 10.1016/j.molcel.2013.04.016. [Epub ahead of print]
PMID: 23685074 [PubMed - as supplied by publisher]