Drosophila emerins control LINC complex localization and transcription to regulate myonuclear position

Mispositioned nuclei are a hallmark of skeletal muscle disease. Many of the genes that are linked to Emery-Dreifuss muscular dystrophy (EDMD) encode proteins that are critical for nuclear movement in various cells, suggesting that disruptions in nuclear movement and position may contribute to disease progression. However, how these genes are coordinated to move nuclei is not known. Here, we focussed on two different emerin proteins in Drosophila, Bocksbeutel and Otefin, and their effects on nuclear movement. Although nuclear position was dependent on both, elimination of either Bocksbeutel or Otefin produced distinct phenotypes that were based in differential effects on the KASH-domain protein Klarsicht. Specifically, loss of Bocksbeutel reduced Klarsicht localization to the nucleus and resulted in a disruption in nuclear separation. Loss of Otefin increased the transcription of Klarsicht and led to premature separation of nuclei and their positioning closer to the edge of the muscle. Consistent with opposing functions, nuclear position is normal in otefin; bocksbeutel double mutants. These data indicate emerin-dependent regulation of Klarsicht levels in the nuclear envelope is a critical determinant of nuclear position.