Molecular and functional analysis of calcium binding by a cancer-linked calreticulin mutant.

CRT Del52 retains similar low-affinity calcium-binding characteristics to wild-type CRT, with residues 340–349 contributing, as measured by isothermal titration calorimetry.

• Why it matters: Mutations in CALR are linked to myeloproliferative neoplasms, and reported ER calcium perturbations raise questions about how mutant CRT affects calcium binding and signaling.
• What they did: Recombinant wild-type CRT and CRT Del52 were compared by ITC, and CRT-KO cells were reconstituted with either protein to assess ER/cytosolic calcium and store-operated calcium entry.
• The result: ER and cytosolic calcium levels and SOCE were comparable in CRT-KO cells expressing wild-type CRT versus CRT Del52, while CRT deficiency increased expression of multiple ER proteins tied to low-affinity calcium binding or ER calcium regulation.

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