Fig. 6: Models explaining how calcimembrin may modulate calcineurin signaling.

a (1) CLMB localizes to membranes via dynamic acylation, where it (2) recruits calcineurin (turquoise). At low CLMB levels, calcineurin remains tightly bound to phosphorylated CLMB (purple) regardless of Ca²⁺ signals. (3) At higher CLMB levels, CLMB (purple and green) forms multimers with calcineurin and is dephosphorylated upon calcineurin activation by Ca²⁺ and CaM. (4) Calcineurin is then released and can engage and dephosphorylate membrane-associated substrates (red) that contain PxIxT and LxVP SLiMs. b (1) CLMB localizes to membranes via dynamic acylation, where it (2) recruits calcineurin (turquoise). At low CLMB levels, calcineurin remains tightly bound to phosphorylated CLMB (purple). (3) Ca²⁺ and CaM activate calcineurin, allowing it to engage and dephosphorylate LxVP-containing substrates (red). (4) At high CLMB levels (purple and green), calcineurin-CLMB multimers form. (5) This promotes CLMB dephosphorylation and triggers calcineurin release to terminate signaling.