Ca2+- and Myristoylation-Dependent Association of Calcineurin with Phosphatidylserine

• Published in: Journal of biochemistry (Tokyo) 2001-05, Vol.129 (5), p.835-841
• Main Authors: Perrino, Brian A., Martin, Brett A.
• Format: Article
• Language: English
• Subjects: calcineurin; calmodulin; membrane; myristoylation; phospholipids
• ISSN: 0021-924X
• DOI: 10.1093/oxfordjournals.jbchem.a002927

It has been proposed that N-terminal myristoylation of calcineurin B is necessary for the membrane association of calcineurin. We tested the effects of Ca2+ and myristoylation on the binding of calcineurin B alone or heterodimeric calcineurin to phosphatidylserine or phosphatidylcholine vesicles. In the presence of excess phosphatidylserine, 50-60% of total calcineurin associated with phosphatidylserine in a Ca2+-sensitive manner. Calcineurin did not associate with phosphatidylcholine. Calcineurin containing both the α and β catalytic subunit isoforms bound to phosphatidylserine. Calmodulin interfered with the association of calcineurin with phosphatidylserine. In the presence of Ca2+, myristoylated calcineurin B alone did not bind to phosphatidylcholine but did bind to phosphatidylserine, although to a lesser extent than the calcineurin hetero-dimer. Non-myristoylated calcineurin B alone, or calcineurin containing non-myristoy-lated calcineurin B did not associate with phosphatidylserine in the presence of Ca2+. These results indicate: (i) Both isoforms of calcineurin bind to phosphatidylserine. (ii) A phospholipid binding site is located on the calcineurin B subunit. (iii) Calcineurin B myristoylation is required for the Ca2+-sensitive binding of calcineurin to phosphatidylserine vesicles in vitro.