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

ABSTRACT: 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-?) interacts with lamin A/C and with several lamin A/C partners involved in striated muscle laminopathies. To determine PKC-?'s involvement in muscular laminopathies, PKC-?'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-? cellular distribution in mutant cells compared to WT. PKC-? activation (phos-PKC-?) was decreased or unchanged in the studied cells expressing LMNA mutations, and the activation of its downstream targets, ERK 1/2, paralleled PKC-? activation alteration. Furthermore, the phos-PKC-?-lamin A/C proximity was altered. Overall, the data showed that PKC-? localization, activation, and proximity with lamin A/C were affected by certain pathogenic LMNA mutations, suggesting PKC-? involvement in striated muscle laminopathies.

SUBMITTER: Nicolas HA 

PROVIDER: S-EPMC7693451 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature