Aplip1 regulates Dynein‐dependent but not Kinesin‐dependent nuclear movement in muscle

Muscle cells are composed of multinucleated cells called myofibers. The nuclei in myofibers undergo a series of dynamic movements to maximize internuclear distance. The importance of these movements is illustrated by the high correlation between mispositioned nuclei and muscle disease. Though the positioning of nuclei is a distinctive feature of the myofiber, the mechanisms for nuclear movement and positioning are only now emerging. It is known that two separate pathways contribute to nuclear movement in muscle. In the cortical pathway, Kinesin moves Dynein to the cell cortex where it is anchored. From that position, Dynein applies a pulling force on nuclei. Additionally, in the proximal pathway, Dynein and Kinesin apply force directly to the nuclei. Although Dynein and Kinesin are required for both pathways, the two pathways are spatially segregated suggesting that separate pools of Dynein and Kinesin must be specified for each pathway. To understand how the two pools of Dynein and Kinesin are differentially regulated, we have tested factors known to regulate motor activity in other contexts. One candidate, Aplip1 has been demonstrated to coordinate Kinesin and Dynein during axonal transport and was therefore a strong candidate to regulate Dynein and Kinesin in muscle. We found that Aplip1‐eGFP localizes at the cortex of the muscle cell, suggesting a role for Aplip1 in the cortical pathway. Consistent with this, embryos that were heterozygous for null mutations in both Aplip1 and Dynein displayed mispositioned nuclei. However, embryos that were heterozygous for null mutations in both Aplip1 and Kinesin were unaffected, suggesting that Aplip1 does not contribute to Kinesin‐dependent trafficking of Dynein. Together, these data suggest that Aplip1 specifically regulates Dynein activity at the cell cortex by a Kinesin‐independent mechanism.