Bmcc 1 s , a novel brain-isoform of Bmcc 1 , affects cell morphology by regulating MAP 6 / STOP functions

The BCH (BNIP2 and Cdc42GAP Homology) domain-containing protein Bmcc1/Prune2 is highly enriched in the brain and is involved in the regulation of cytoskeleton dynamics and cell survival. However, the molecular mechanisms accounting for these functions are poorly defined. Here, we have identified Bmcc1s, a novel isoform of Bmcc1 predominantly expressed in the mouse brain. In primary cultures of astrocytes and neurons, Bmcc1s localized on intermediate filaments and microtubules and interacted directly with MAP6/STOP, a microtubule-binding protein responsible for microtubule cold stability. Bmcc1s overexpression inhibited MAP6-induced microtubule cold stability by displacing MAP6 away from microtubules. It also resulted in the formation of membrane protrusions for which MAP6 was a necessary cofactor of Bmcc1s. This study identifies Bmcc1s as a new MAP6 interacting protein able to modulate MAP6-induced microtubule cold stability. Moreover, it illustrates a novel mechanism by which Bmcc1 regulates cell morphology. Citation: Arama J, Boulay A-C, Bosc C, Delphin C, Loew D, et al. (2012) Bmcc1s, a Novel Brain-Isoform of Bmcc1, Affects Cell Morphology by Regulating MAP6/ STOP Functions. PLoS ONE 7(4): e35488. doi:10.1371/journal.pone.0035488 Editor: Gilbert Bernier, University of Montréal and Hôpital Maisonneuve-Rosemont, Canada Received November 29, 2011; Accepted March 16, 2012; Published April 16, 2012 Copyright: 2012 Arama et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by Agence Nationale pour la Recherche ANR-programme blanc Neurosciences. The Laboratory of Proteomic Mass Spectrometry is supported by ‘‘Cancéropôle Ile-de-France’’ and ‘‘‘l’Institut National du Cancer’’. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: martine.cohen-salmon@college-de-france.fr . These authors contributed equally to this work. " These authors also contributed equally to this work. ¤ Current address: Department of pharmacology, School of Pharmacy, London, United Kingdom