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

Mencarelli, C; Nitarska, J; Kroecher, T; Ferraro, F; Massey, K; Riccio, A; Pichaud, F; (2018) RanBP1 Couples Nuclear Export and Golgi Regulation through LKB1 to Promote Cortical Neuron Polarity. Cell Reports , 24 (10) 2529-2539.e4. 10.1016/j.celrep.2018.07.107. Green open access

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Abstract

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.

Type: Article
Title: RanBP1 Couples Nuclear Export and Golgi Regulation through LKB1 to Promote Cortical Neuron Polarity
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2018.07.107
Publisher version: https://doi.org/10.1016/j.celrep.2018.07.107
Language: English
Additional information: © 2018 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: LKB1, Ran, RanBP1, STK25, axon, axonogenesis, neuron polarity, nuclear export
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10055831
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