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Molecular and Cellular Biology, February 2009, p. 726-735, Vol. 29, No. 3
0270-7306/09/$08.00+0     doi:10.1128/MCB.01180-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Protein Kinase KIS Localizes to RNA Granules and Enhances Local Translation{triangledown}

Serafí Cambray,{ddagger} Neus Pedraza,{ddagger} Marta Rafel, Eloi Garí, Martí Aldea, and Carme Gallego*

Departament de Ciències Mèdiques Bàsiques, IRBLLEIDA, Universitat de Lleida, Montserrat Roig, 2, 25008 Lleida, Catalonia, Spain

Received 26 July 2008/ Returned for modification 22 August 2008/ Accepted 10 November 2008

The regulation of mRNA transport is a fundamental process for cytoplasmic sorting of transcripts and spatially controlled translational derepression once properly localized. There is growing evidence that translation is locally modulated as a result of specific synaptic inputs. However, the underlying molecular mechanisms that regulate this translational process are just emerging. We show that KIS, a serine/threonine kinase functionally related to microtubule dynamics and axon development, interacts with three proteins found in RNA granules: KIF3A, NonO, and eEF1A. KIS localizes to RNA granules and colocalizes with the KIF3A kinesin and the β-actin mRNA in cultured cortical neurons. In addition, KIS is found associated with KIF3A and 10 RNP-transported mRNAs in brain extracts. The results of knockdown experiments indicate that KIS is required for normal neurite outgrowth. More important, the kinase activity of KIS stimulates 3' untranslated region-dependent local translation in neuritic projections. We propose that KIS is a component of the molecular device that modulates translation in RNA-transporting granules as a result of local signals.

* Corresponding author. Mailing address: Departament de Ciències Mèdiques Bàsiques, IRBLLEIDA, Universitat de Lleida, Montserrat Roig, 2, 25008 Lleida, Catalonia, Spain. Phone: 34 973702438. Fax: 34 973702426. E-mail: carme.gallego{at}cmb.udl.cat

{triangledown} Published ahead of print on 17 November 2008.

{ddagger} S.C. and N.P. contributed equally to this work.

Molecular and Cellular Biology, February 2009, p. 726-735, Vol. 29, No. 3
0270-7306/09/$08.00+0     doi:10.1128/MCB.01180-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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