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Gavilan, M. P.

Publications and source records attributed to Gavilan, M. P..

2 recordsLinked to original sources

Regulation of mitochondrial dynamics by Aurora A kinase

Aurora A kinase (AURKA) is a major regulator of mitosis and an important driver of cancer progression. The roles of AURKA outside of mitosis, and how these might contribute to cancer progression, are not well understood. Here we show that a fraction of cytoplasmic AURKA is associated with mitochondria, co-fractionating in cell extracts and interacting with mitochondrial proteins by reciprocal co-immunoprecipitation. We have also found that the dynamics of the mitochondrial network are sensitive to AURKA inhibition, depletion or overexpression. This can account for the different mitochondrial morphologies observed in RPE1 and U2OS cell lines, which show very different levels of expression of AURKA. We identify the mitochondrial fraction of AURKA as influencing mitochondrial morphology, since an N-terminally truncated version of the kinase that does not localize to mitochondria does not affect the mitochondrial network. We identify a cryptic mitochondrial targeting sequence in the AURKA N-terminus and discuss how alternative conformations of the protein may influence its cytoplasmic fate.

cell biology

The Centrosome Controls the Number and Spatial Distribution of Microtubules by Negatively Regulating Alternative MTOCs

In this work, we have investigated in mammalian cells how microtubule nucleation at centrosome and Golgi apparatus are coordinated, using genetic ablation of three {gamma}-TuRC binding proteins -AKAP450, Pericentrin and CDK5Rap2- and the PLK4 inhibitor centrinone. We show that centrosomal microtubule nucleation is independent of Golgi activity whereas the converse is not true: nucleation on the Golgi negatively correlates with the number of centrosomes. In addition, depleting AKAP450 in cells lacking centrioles, that abolishes Golgi nucleation activity, leads to microtubule nucleation from numerous cytoplasmic Golgi-unbound acentriolar structures containing Pericentrin, CDK5Rap2 and y-tubulin. Strikingly, centrosome-less cells display twice higher microtubule density than normal cells, suggesting that the centrosome controls the spatial distribution of microtubules, not only by nucleating them, but also by acting as a negative regulator of alternative MTOCs. Collectively, the data reveals a hierarchical control of microtubule nucleation, with the centrosome regulating this process in a more complex manner than usually thought. It also unveils mechanisms that could help understanding MT network reorganization during cell differentiation.

cell biology