Differential effects of the Rac GTPase on Purkinje cell axons and dendritic trunks and spines

Abstract

NEURONS contain distinct compartments including dendrites, dendritic spines, axons and synaptic terminals¹. The molecular mechanisms that generate and distinguish these compartments, although largely unknown, may involve the small GTPases Rac and Cdc42 (ref. 2), which appear to regulate actin polymerization³. Having shown that perturbations of Racl activity block the growth of axons but not dendrites of Drosophila neurons², we investigated whether this also applies to mammals by examining transgenic mice expressing constitutively active human Racl in Purkinje cells. We found that these mice were ataxic and had a reduction of Purkinje-cell axon terminals in the deep cerebellar nuclei, whereas the dendritic trees grew to normal height and branched extensively. Unexpectedly, the dendritic spines of Purkinje cells in developing and mature cerebella were much reduced in size but increased in number. These 'mini' spines often form supernumerary synapses. These differential effects of perturbing Racl activity indicate that there may be distinct mechanisms for the elaboration of axons, dendrites and dendritic spines.