Microtubules orchestrate local translation to enable cardiac growth

Hypertension, exercise, and pregnancy are common triggers of cardiac remodeling, which occurs primarily through the hypertrophy of individual cardiomyocytes. During hypertrophy, stress-induced signal transduction increases cardiomyocyte transcription and translation, which promotes the addition of new contractile units through poorly understood mechanisms. The cardiomyocyte microtubule network is also implicated in hypertrophy, but via an unknown role. Here, we show that microtubules are indispensable for cardiac growth via spatiotemporal control of the translational machinery. We find that the microtubule motor Kinesin-1 distributes mRNAs and ribosomes along microtubule tracks to discrete domains within the cardiomyocyte. Upon hypertrophic stimulation, microtubules redistribute mRNAs and new protein synthesis to sites of growth at the cell periphery. If the microtubule network is disrupted, mRNAs and ribosomes collapse around the nucleus, which results in mislocalized protein synthesis, the rapid degradation of new proteins, and a failure of growth, despite normally increased translation rates. Together, these data indicate that mRNAs and ribosomes are actively transported to specific sites to facilitate local translation and assembly of contractile units, and suggest that properly localized translation - and not simply translation rate - is a critical determinant of cardiac hypertrophy. In this work, we find that microtubule based-transport is essential to couple augmented transcription and translation to productive cardiomyocyte growth during cardiac stress.

Automated summary

Cardiac remodeling is triggered by hypertension, exercise, and pregnancy, and mainly occurs through hypertrophy of individual cardiomyocytes. Microtubules play a crucial role in cardiac growth by controlling the spatiotemporal translation machinery and distributing mRNA and ribosomes to specific locations within cardiomyocytes during hypertrophic stimulation. Disruption of the microtubule network leads to mislocalized protein synthesis, degradation of new proteins, and inhibition of growth, highlighting the importance of properly localized translation for cardiac hypertrophy.