From: Department of Biological Sciences, Osaka University, Japan

Will give a seminar entitled:

Cell chirality and its molecular origins: a key to left-right asymmetric development

Chirality is a fundamental problem in biology, from the molecular to individual levels. An object is chiral if it cannot be superposed on its mirror image. Animals show chirality in left-right (LR) asymmetric structures of their bodies. We demonstrated that chirality at the cellular level, designated as “cell chirality,” generates mechanical force with chirality, which consequently drives LR-asymmetric morphogenesis of various organs in Drosophila.

In Drosophila, two Myosin Is, Myosin IC (MyoIC) and Myosin ID (MyoID) have activities to switch body and cell chirality to left- and right-handed states, respectively. Given that Myosin Is are actin-based motor proteins, we speculated that they may induce F-actin motion with chirality. Recently, we revealed that Drosophila macrophages showed cell chirality in the vortex flow of F-action around the nucleus. MyoIC and MyoID accelerated counterclockwise (left-handed) and clockwise (right-handed) rotational movements of F-actin, respectively. Using a modified in vitro gliding assay, we showed that MyoID, but not MyoIC, organizes F-actin into a ring-like structure of single-cell size rotating clockwise (designated as chiral actin ring), which is probably equivalent to clockwise rotating F-actin flow in macrophages.

We identified the motifs that carry information dictating cell chirality in Myosin Is. Loop motifs in the head domain of MyoIC, but not MyoID, were responsible for dictating the respective chirality of the cell and body. In addition, our in vivoanalyses using myosins from various species, including plants, showed that the activity to form a chiral actin ring, as found in MyoID, is a key dictating the right-handed chirality in cells and the body. Therefore, our results demonstrate that MyoIC and MyoID dictate the left- and right-handed states of cell chirality, respectively, through two distinct molecular mechanisms, involving loop motifs or chiral actin rings. We speculate that distinctive chiral structures in the head domains of MyoIC and MyoID are responsible for these two different mechanisms.

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