Localized translation and sarcomere maintenance requires ribosomal protein SA in mice.

Cardiomyocyte sarcomeres contain localized ribosomes, but the factors responsible for their localization and the significance of localized translation are unknown. Using proximity labeling, we identified ribosomal protein SA (RPSA) as a Z-line protein. In cultured cardiomyocytes, the loss of RPSA led to impaired local protein translation and reduced sarcomere integrity. By employing CAS9-expressing mice, along with adeno-associated viruses expressing CRE recombinase and single-guide RNAs targeting Rpsa, we knocked out Rpsa in vivo and observed mislocalization of ribosomes and diminished local translation. These genetic mosaic mice with Rpsa knockout in a subset of cardiomyocytes developed dilated cardiomyopathy, featuring atrophy of RPSA-deficient cardiomyocytes, compensatory hypertrophy of unaffected cardiomyocytes, left ventricular dilation, and impaired contractile function. We demonstrated that RPSA C-terminal domain is sufficient for localization to the Z-lines and that if the microtubule network is disrupted RPSA loses its sarcomeric localization. These findings highlight RPSA as a ribosomal factor essential for ribosome localization to the Z-line, facilitating local translation and sarcomere maintenance.

Coordination between cytoskeletal organization, cell contraction and extracellular matrix development, is depended on LOX for aneurysm prevention.

Distinct, seemingly independent, cellular pathways affecting intracellular machineries or extracellular matrix (ECM) deposition and organization, have been implicated in aneurysm formation. One of the key genes associated with the pathology in both humans and mice is Lysyl oxidase (LOX), a secreted ECM-modifying enzyme, highly expressed in medial vascular smooth muscle cells. To dissect the mechanisms leading to aneurysm development, we conditionally deleted Lox in smooth muscle cells. We find that cytoskeletal organization is lost following Lox deletion. Cell culture assays and in vivo analyses demonstrate a cell-autonomous role for LOX affecting myosin light chain phosphorylation and cytoskeletal assembly resulting in irregular smooth muscle contraction. These results not only highlight new intracellular roles for LOX, but notably they link between multiple processes leading to aneurysm formation suggesting LOX coordinates ECM development, cytoskeletal organization and cell contraction required for media development and function.

Dripping faucet dynamics is determined by synchronization of drop oscillations and detachment.

A dripping faucet is an example of an everyday system that exhibits surprisingly rich dynamics ranging from periodic to chaotic. Using a simple capacitive device, we experimentally demonstrate that the dynamics is determined by the degree of synchronization between two temporally disparate processes: the time at which a drop attains a critical mass and an oscillatory process that accompanies the formation of a drop. We present a full experimental phase-space reconstruction of the ensuing dynamics.