CapZ integrates several signaling pathways in response to mechanical stiffness

The Journal of General Physiology
Christopher Solís, Brenda Russell

Abstract

Muscle adaptation is a response to physiological demand elicited by changes in mechanical load, hormones, or metabolic stress. Cytoskeletal remodeling processes in many cell types are thought to be primarily regulated by thin filament formation due to actin-binding accessory proteins, such as the actin-capping protein. Here, we hypothesize that in muscle, the actin-capping protein (named CapZ) integrates signaling by a variety of pathways, including phosphorylation and phosphatidylinositol 4,5-bisphosphate (PIP2) binding, to regulate muscle fiber growth in response to mechanical load. To test this hypothesis, we assess mechanotransduction signaling that regulates muscle growth using neonatal rat ventricular myocytes cultured on substrates with the stiffness of the healthy myocardium (10 kPa), fibrotic myocardium (100 kPa), or glass. We investigate how PIP2 signaling affects CapZ using the PIP2 sequestering agent neomycin and the effect of PKC-mediated CapZ phosphorylation using the PKC-activating drug phorbol 12-myristate 13-acetate (PMA). Molecular simulations suggest that close interactions between PIP2 and the β-tentacle of CapZ are modified by phosphorylation at T267. Fluorescence recovery after photobleaching (FRAP) demons...Continue Reading

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Citations

Apr 17, 2019·The Journal of General Physiology·Henk L Granzier, Richard L Moss
Jan 1, 2021·Frontiers in Cell and Developmental Biology·Amanda KrajnikYongho Bae
Mar 20, 2021·The Journal of General Physiology·Christopher Solís, R John Solaro
May 25, 2021·Frontiers in Cellular Neuroscience·Anchel González-BarrigaMário Gomes-Pereira

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Methods Mentioned

BETA
acetylation
PMA
FRET
Fluorescence
pull-down

Software Mentioned

Autodock Vina
ImageJ
PyRx
AMBER
UCSF Chimera
CapZ
MATLAB

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Actin-binding Proteins

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