Multiple Zippers

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Science  01 Jun 2001:
Vol. 292, Issue 5522, pp. 1613
DOI: 10.1126/science.292.5522.1613c

Ryanodine receptors (RyRs) are calcium channels essential for proper excitation-contraction coupling in muscle. Phosphorylation modulates the channel properties of these receptors, and elevated phosphorylation of RyR2 (the cardiac form of RyR) is associated with heart failure.

Marks et al. show that RyR2 has three leucine/isoleucine zipper (LZ) motifs, each of which interacts with a distinct cellular regulator. LZ1 mediates binding of protein phosphatase 1 (PP1) through the PP1-targeting protein spinophilin; LZ2 mediates binding of PP2A through the PP2A-targeting protein PR130; and LZ3 mediates binding of the cyclic AMP-dependent protein kinase through the A-kinase anchoring protein (AKAP). Disruption of the LZ-mediated interactions resulted in changes in RyR channel activity and altered regulation by phosphorylation. These results enabled Marks et al. to predict kinase and phosphatase interactions with RyR1 (the skeletal form of RyR) and may facilitate identification of regulatory components in other channel complexes. — NG

J. Cell Biol.153, 699 (2001).

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