Microtubule dynamics control the direction of cardiomyocyte growth

• 成果类型: Article
• 署名作者: Scarborough, Emily A.; Randell, Rani M.; Uchida, Keita; Stone, Kathlyene R.; Margulies, Kenneth B.; Prosser, Benjamin L.
• 署名单位: University of Pennsylvania; Pennsylvania Medicine; University of Pennsylvania; University of Pennsylvania; Oakland University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adz1970
• 发表日期: 2026-05-14
• 页码: eadz1970
• 关键词: TRANSITIONAL JUNCTION; BILIARY-EXCRETION; nuclear-envelope; proteins; pressure; heart; stabilization; localization; paclitaxel; hypothesis

摘要

The adult heart grows by the addition of sarcomeres along the length or width of individual cardiomyocytes, yet how directional growth is spatially coordinated remains unclear. We found that microtubule dynamics could act as a toggle to direct cardiomyocyte growth. Increasing microtubule stability drove cellular widening, concomitant with redirecting messenger RNa (mRNa) export and translation along the width of the cell and reinforcement of the intercalated disc. Conversely, decreasing microtubule stability promoted cellular lengthening, disrupting the intercalated disc and biasing translation and incorporation of new sarcomeric protein toward this structure. Notably, disrupting intercalated disc adhesion was sufficient for cardiomyocyte elongation yet dispensable for cardiomyocyte widening. Thus, the heart coordinates local translation and structural remodeling to orchestrate bidirectional growth.