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Abstract
Aurora kinases are key proteins found throughout the eukaryotes that control mitotic progression. Vertebrate Aurora-A and B kinases are thought to have evolved from a single Aurora-kinase isoform closest to that found in present day urochordates. In urochordate ascidians Aurora binds both TPX2 (a vertebrate AURKA partner) and INCENP (a vertebrate AURKB partner) and localizes to centrosomes and spindle microtubules as well as chromosomes and midbody during both meiosis and mitosis. Ascidian Aurora also displays this localization pattern during mitosis in echinoderms, strengthening the idea that non-vertebrate deuterostomes such as the urochordates and echinoderms possess a single form of Aurora kinase that has properties of vertebrate Aurora-kinase A and B. In the ascidian, TPX2 localizes to the centrosome and the spindle poles also as in vertebrates. However, we were surprised to find that TPX2 also localized strongly to the midbody in ascidian eggs and embryos. We thus examined more closely Aurora localization to the midbody by creating two separate point mutations of ascidian Aurora predicted to perturb binding to TPX2. Both forms of mutated Aurora behaved as predicted: neither localized to spindle poles where TPX2 is enriched. Interestingly, neither form of mutated Aurora localized to the midbody where TPX2 is also enriched, suggesting that ascidian Aurora midbody localization required TPX2 binding in ascidians. Functional analysis revealed that inhibition of Aurora kinase with a pharmacological inhibitor or with a dominant negative kinase dead form of Aurora caused cytokinesis failure and perturbed midbody formation during polar body extrusion. Our data support the view that vertebrate Aurora-A and B kinases evolved from a single non-vertebrate deuterostome ancestor. Moreover, since TPX2 localizes to the midbody in ascidian eggs and cleavage stage embryos it may be worthwhile re-assessing whether Aurora A kinase or TPX2 localize to the midbody in eggs and cleavage stage embryos.
Highlights
Cell division is controlled by key protein kinases including cyclin-dependent kinase 1 (Cdk1), polo like kinases (Plk) and Aurora kinases
To our surprise we found that TPX2 localizes to the midbody in urochordate ascidian embryos, suggesting that vertebrate Aurora A and B differential subcellular localization pattern is in part brought about because vertebrate TPX2 lost the ability to localize to the midbody
In order to investigate the localization of the unique isoform of Aurora in ascidians, we studied the localization of endogenous Aurora and compared it with the localization pattern observed with Aurora fluorescent fusion protein constructs (Venus and mCherry) during meiotic and mitotic cell cycles in cleaving embryos
Summary
Cell division is controlled by key protein kinases including cyclin-dependent kinase 1 (Cdk1), polo like kinases (Plk) and Aurora kinases. These kinases control the orderly processes of nuclear envelope breakdown, chromosome condensation, mitotic spindle formation, kinetochore-microtubule attachment and cytokinesis (reviewed by [1]). In vertebrates Aurora-A kinase localizes to spindle microtubules through association with TPX2 (Targeting protein for Xenopus kinesin-like protein 2) [4]. Aurora-B kinase binds INCENP and is part of the chromosomal passenger complex (CPC) which moves from the inner kinetochore to the central spindle and midbody at anaphase [5]. It has yet to be tested, it is possible that the ancestor of vertebrate Aurora-A and B kinase could bind to either TPX2 or INCENP, thereby explaining how starfish Aurora-kinase displays both an Aurora-A and B kinase localization pattern
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