Protein Kinase C Alpha Cellular Distribution, Activity, and Proximity with Lamin A/C in Striated Muscle Laminopathies

Striated muscle laminopathies are cardiac and skeletal muscle conditions caused by mutations in the lamin A/C gene (LMNA). LMNA codes for the A-type lamins, which are nuclear intermediate filaments that maintain the nuclear structure and nuclear processes such as gene expression. Protein kinase C alpha (PKC-alpha) interacts with lamin A/C and with several lamin A/C partners involved in striated muscle laminopathies. To determine PKC-alpha's involvement in muscular laminopathies, PKC-alpha's localization, activation, and interactions with the A-type lamins were examined in various cell types expressing pathogenic lamin A/C mutations. The results showed aberrant nuclear PKC-alpha cellular distribution in mutant cells compared to WT. PKC-alpha activation (phos-PKC-alpha) was decreased or unchanged in the studied cells expressing LMNA mutations, and the activation of its downstream targets, ERK 1/2, paralleled PKC-alpha activation alteration. Furthermore, the phos-PKC-alpha-lamin A/C proximity was altered. Overall, the data showed that PKC-alpha localization, activation, and proximity with lamin A/C were affected by certain pathogenic LMNA mutations, suggesting PKC-alpha involvement in striated muscle laminopathies.