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Original Article |
Correspondence to: John A. Cooper, Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110. Tel:(314) 362-3964 Fax:(314) 362-0098 E-mail:jcooper{at}cellbio.wustl.edu.
Actin capping protein (CP) binds barbed ends of actin filaments to regulate actin assembly. CP is an 
/ß heterodimer. Vertebrates have conserved isoforms of each subunit. Muscle cells contain two ß isoforms. ß1 is at the Z-line; ß2 is at the intercalated disc and cell periphery in general. To investigate the functions of the isoforms, we replaced one isoform with another using expression in hearts of transgenic mice.
Mice expressing ß2 had a severe phenotype with juvenile lethality. Myofibril architecture was severely disrupted. The ß2 did not localize to the Z-line. Therefore, ß1 has a distinct function that includes interactions at the Z-line. Mice expressing ß1 showed altered morphology of the intercalated disc, without the lethality or myofibril disruption of the ß2-expressing mice.
The in vivo function of CP is presumed to involve binding barbed ends of actin filaments. To test this hypothesis, we expressed a ß1 mutant that poorly binds actin. These mice showed both myofibril disruption and intercalated disc remodeling, as predicted.
Therefore, CPß1 and CPß2 each have a distinct function that cannot be provided by the other isoform. CPß1 attaches actin filaments to the Z-line, and CPß2 organizes the actin at the intercalated discs.
Key Words: isoform, heart, cardiomyopathy, Z line, sarcomere
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