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Title: Competition between kinesin-1 and myosin-V defines Drosophila posterior determination. Author: Lu W, Lakonishok M, Liu R, Billington N, Rich A, Glotzer M, Sellers JR, Gelfand VI. Journal: Elife; 2020 Feb 14; 9():. PubMed ID: 32057294. Abstract: Local accumulation of oskar (osk) mRNA in the Drosophila oocyte determines the posterior pole of the future embryo. Two major cytoskeletal components, microtubules and actin filaments, together with a microtubule motor, kinesin-1, and an actin motor, myosin-V, are essential for osk mRNA posterior localization. In this study, we use Staufen, an RNA-binding protein that colocalizes with osk mRNA, as a proxy for osk mRNA. We demonstrate that posterior localization of osk/Staufen is determined by competition between kinesin-1 and myosin-V. While kinesin-1 removes osk/Staufen from the cortex along microtubules, myosin-V anchors osk/Staufen at the cortex. Myosin-V wins over kinesin-1 at the posterior pole due to low microtubule density at this site, while kinesin-1 wins at anterior and lateral positions because they have high density of cortically-anchored microtubules. As a result, posterior determinants are removed from the anterior and lateral cortex but retained at the posterior pole. Thus, posterior determination of Drosophila oocytes is defined by kinesin-myosin competition, whose outcome is primarily determined by cortical microtubule density. One of the most fundamental steps of embryonic development is deciding which end of the body should be the head, and which should be the tail. Known as 'axis specification', this process depends on the location of genetic material called mRNAs. In fruit flies, for example, the tail-end of the embryo accumulates an mRNA called oskar. If this mRNA is missing, the embryo will not develop an abdomen. The build-up of oskar mRNA happens before the egg is even fertilized and depends on two types of scaffold proteins in the egg cell called microtubules and microfilaments. These scaffolds act like ‘train tracks’ in the cell and have associated protein motors, which work a bit like trains, carrying cargo as they travel up and down along the scaffolds. For microtubules, one of the motors is a protein called kinesin-1, whereas for microfilaments, the motors are called myosins. Most microtubules in the egg cell are pointing away from the membrane, while microfilament tracks form a dense network of randomly oriented filaments just underneath the membrane. It was already known that kinesin-1 and a myosin called myosin-V are important for localizing oskar mRNA to the posterior of the egg. However, it was not clear why the mRNA only builds up in that area. To find out, Lu et al. used a probe to track oskar mRNA, while genetically manipulating each of the motors so that their ability to transport cargo changed. Modulating the balance of activity between the two motors revealed that kinesin-1 and myosin-V engage in a tug-of-war inside the egg: myosin-V tries to keep oskar mRNA underneath the membrane of the cell, while kinesin-1 tries to pull it away from the membrane along microtubules. The winner of this molecular battle depends on the number of microtubule tracks available in the local area of the cell. In most parts of the cell, there are abundant microtubules, so kinesin-1 wins and pulls oskar mRNA away from the membrane. But at the posterior end of the cell there are fewer microtubules, so myosin-V wins, allowing oskar mRNA to localize in this area. Artificially 'shaving' some microtubules in a local area immediately changed the outcome of this tug-of-war creating a build-up of oskar mRNA in the 'shaved' patch. This is the first time a molecular tug-of-war has been shown in an egg cell, but in other types of cell, such as neurons and pigment cells, myosins compete with kinesins to position other molecular cargoes. Understanding these processes more clearly sheds light not only on embryo development, but also on cell biology in general.[Abstract] [Full Text] [Related] [New Search]