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SERCA's calcium pumping ability is reduced by the ERp57 chaperone.

ER chaperones need calcium to help them in their folding duties. Work on page 35 by Li and Camacho shows that some chaperones take a proactive stance on Ca²⁺ levels by regulating an ER Ca²⁺ pump.

Calcium must be pumped into the ER from the cytoplasm to maintain high levels for Ca²⁺-needy chaperones. This function is performed in many cells by the SERCA 2b pump. The authors show that some chaperones, in addition to helping newly synthesized proteins fold correctly, also inform SERCA 2b of the ER Ca²⁺ status. And what they have to say can alter pump activity.

High Ca²⁺ levels lowered pump activity by promoting an interaction between SERCA 2b and the chaperone ERp57, which catalyzed disulfide bridge formation in the lumenal portion of SERCA 2b. But the SERCA–ERp57 interaction was lost at lower ER Ca²⁺ concentrations. This reduced the disulfide bridge and converted the pump into its most active form. The ER is naturally an oxidizing environment, suggesting that a reductase may act on SERCA 2b unless ERp57 gets in the way.

Another chaperone, calreticulin (CRT), was needed for the ERp57–SERCA 2b interaction. CRT binds to both ERp57 and SERCA 2b, and SERCA 2b mutants that did not bind to CRT were not inhibited by ERp57. Thus, it is possible that CRT may be the actual calcium sensor—bringing ERp57 to SERCA only when Ca²⁺ levels are high enough and removing ERp57 when Ca²⁺ levels are lowered so that the stores are rapidly refilled.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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Ca²⁺-dependent redox modulation of SERCA 2b by ERp57

Yun Li and Patricia Camacho
J. Cell Biol. 2004 164: 35-46. [Abstract] [Full Text] [PDF]

This Article PDF (Full Text) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Related Collections Related Article Social Bookmarking                      What's this?