ERp44 and ERGIC-53 synergize in coupling efficiency and fidelity of IgM polymerization and secretion.

Traffic
Margherita Cortini, Roberto Sitia

Abstract

Owing to the quality control mechanisms operating in the early secretory compartment, only native proteins are secreted. Despite the difficulties in assembling planar immunoglobulin M (IgM) polymers, antibody-secreting cells can release up to thousands of IgM per second. The finding that secretory micro (micro(s)) chains bind to ERGIC-53, a lectin transporter that cycles in the early secretory compartment, suggested that ERGIC-53 hexamers could provide a polymerization platform. Here,we show that ERGIC-53 binds to the conserved Asn563 glycan in the C-terminal micro(s) tailpiece (micro(s)tp). Removal of this glycan inhibits ERGIC-53 binding and results in the rapid formation of larger polymeric assemblies. In contrast, removal of the Asn402 oligosaccharides prevents both polymerization and secretion. ERp44,a chaperone that interacts with ERGIC-53, binds to Cys575 in the micro(s)tp, providing a fail-safe mechanism that retrieves unpolymerized IgM subunits and promotes polymerization. The coordinated action of ERGIC-53 and ERp44 provides a way to improve the efficiency of IgM secretion without perturbing its fidelity.

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Citations

Aug 23, 2011·Antioxidants & Redox Signaling·Tiziana AnelliRoberto Sitia
Mar 1, 2012·Antioxidants & Redox Signaling·Éva MargittaiGábor Bánhegyi
Jan 11, 2012·Antioxidants & Redox Signaling·Masatoshi Hagiwara, Kazuhiro Nagata
Aug 31, 2011·Cold Spring Harbor Perspectives in Biology·Kazutaka Araki, Kazuhiro Nagata
Nov 5, 2010·Diabetes, Obesity & Metabolism·M Cortini, R Sitia
Jun 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Roger MüllerJohannes Buchner
Jan 14, 2012·Biochimica Et Biophysica Acta·Yukiko KamiyaKoichi Kato
Feb 25, 2010·Seminars in Cell & Developmental Biology·Tiziana Anelli, Roberto Sitia
Jun 6, 2015·Biochemical and Biophysical Research Communications·Yan ChangGuangju Ji
May 19, 2010·Traffic·Veronika ReitererHans-Peter Hauri
Feb 8, 2014·Current Biology : CB·Yosef Geva, Maya Schuldiner
Feb 4, 2014·International Journal of Cell Biology·Tiziana Anelli, Eelco van Anken
Mar 7, 2015·Free Radical Biology & Medicine·Tiziana AnelliRoberto Sitia
Dec 15, 2010·Current Opinion in Cell Biology·Matthias J Feige, Linda M Hendershot
Jun 15, 2016·Annual Review of Cell and Developmental Biology·Charles Barlowe, Ari Helenius
Oct 5, 2017·Proceedings of the National Academy of Sciences of the United States of America·Dzana PasalicJohannes Buchner
Dec 3, 2016·The Journal of Cell Biology·Natalia Gomez-Navarro, Elizabeth Miller
Feb 6, 2017·Journal of Cell Science·Donatella GalganoCosima T Baldari
Jul 1, 2020·The Journal of Clinical Investigation·Lakshya BajajMarco Sardiello
Sep 26, 2020·Cells·Chaitanya PatelGerardo Z Lederkremer
Sep 3, 2018·Histochemistry and Cell Biology·Jaakko Saraste, Michaël Marie
Nov 12, 2020·Journal of Cell Science·Tiziana Tempio, Tiziana Anelli
Aug 7, 2014·Journal of Cell Science·Sara SanninoRoberto Sitia

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