RanBP1 Couples Nuclear Export and Golgi Regulation through LKB1 to Promote Cortical Neuron Polarity.

Autor:	Mencarelli C; Medical Research Council Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK., Nitarska J; Medical Research Council Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK., Kroecher T; Medical Research Council Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK., Ferraro F; Medical Research Council Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK., Massey K; Medical Research Council Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK., Riccio A; Medical Research Council Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK., Pichaud F; Medical Research Council Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK. Electronic address: f.pichaud@ucl.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2018 Sep 04; Vol. 24 (10), pp. 2529-2539.e4.
DOI:	10.1016/j.celrep.2018.07.107
Abstrakt:	Neuronal polarity in the developing cortex begins during the early stages of neural progenitor migration toward the cortical plate and culminates with the specification of the axon and dendrites. Here, we demonstrate that the Ran-dependent nucleocytoplasmic transport machinery is essential for the establishment of cortical neuron polarity. We found that Ran-binding protein 1 (RanBP1) regulates axon specification and dendritic arborization in cultured neurons in vitro and radial neural migration in vivo. During axonogenesis, RanBP1 regulates the cytoplasmic levels of the polarity protein LKB1/Par4, and this is dependent on the nuclear export machinery. Our results show that downstream of RanBP1, LKB1 function is mediated by the STK25-GM130 pathway, which promotes axonogenesis through Golgi regulation. Our results indicate that the nucleocytoplasmic transport machinery is a main regulator of neuron polarity, including radial migration, and that the regulated export of LKB1 through RanBP1 is a limiting step of axonogenesis. (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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