Journal Article

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

Wu, Wen Yu, Akimenko, Marie-Andrée, Bertrand, Anne T., Labib, Sarah, Nicolas, Hannah A., Bonne, Gisèle, Bilińska, Zofia T., Tesson, Frédérique, Mohamed-Uvaize, Musfira, Bolongo, Pierrette M.

2020

Overview

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

• Publisher: MDPI AG,MDPI
• Subject: Animal biology / Biochemistry / Biochemistry, Molecular Biology / Cellular Biology / DCM / Development and progression / EDMD / Genetics / Intermediate filament proteins / L-CMD / lamin A/C / Life Sciences / Molecular biology / Muscle diseases / Physiological aspects / protein kinase C alpha / Protein kinases / striated muscle laminopathies