P-Rex2 regulates Purkinje cell dendrite morphology and motor coordination

Donald, S., Humby, Trevor ORCID: https://orcid.org/0000-0002-1840-1799, Fyfe, I., Segonds-Pichon, A., Walker, S. A., Andrews, S. R., Coadwell, W. J., Emson, P., Wilkinson, Lawrence Stephen ORCID: https://orcid.org/0000-0002-9337-6124 and Welch, H. C. E. 2008. P-Rex2 regulates Purkinje cell dendrite morphology and motor coordination. Proceedings of the National Academy of Sciences of the United States of America 105 (11) , pp. 4483-4488. 10.1073/pnas.0712324105

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Abstract

The small GTPase Rac controls cell morphology, gene expression, and reactive oxygen species formation. Manipulations of Rac activity levels in the cerebellum result in motor coordination defects, but activators of Rac in the cerebellum are unknown. P-Rex family guanine-nucleotide exchange factors activate Rac. We show here that, whereas P-Rex1 expression within the brain is widespread, P-Rex2 is specifically expressed in the Purkinje neurons of the cerebellum. We have generated P-Rex2−/− and P-Rex1−/−/P-Rex2−/− mice, analyzed their Purkinje cell morphology, and assessed their motor functions in behavior tests. The main dendrite is thinned in Purkinje cells of P-Rex2−/− pups and dendrite structure appears disordered in Purkinje cells of adult P-Rex2−/− and P-Rex1−/−/P-Rex2−/− mice. P-Rex2−/− mice show a mild motor coordination defect that progressively worsens with age and is more pronounced in females than in males. P-Rex1−/−/P-Rex2−/− mice are ataxic, with reduced basic motor activity and abnormal posture and gait, as well as impaired motor coordination even at a young age. We conclude that P-Rex1 and P-Rex2 are important regulators of Purkinje cell morphology and cerebellar function.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	B Philosophy. Psychology. Religion > BF Psychology Q Science > QP Physiology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	G protein-coupled receptor ; guanine-nucleotide exchange factor ; phosphoinositide-3-kinase ; small GTPase Rac ; ataxia.
Publisher:	National Academy of Sciences
ISSN:	0027-8424
Last Modified:	18 Oct 2022 12:54
URI:	https://orca.cardiff.ac.uk/id/eprint/11545

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