ARF6 in the nervous system

Actin cytoskeleton dynamics and membrane trafficking are tightly connected and are among the most important driving forces of neuronal development, basic synaptic transmission events, and synaptic plasticity. One group of proteins involved in coordination of these two processes is the family of ADP ribosylation factors (ARFs) regulating actin dynamics, lipid modification and membrane trafficking. ARF6 is the only member of the ARF family that can simultaneously regulate actin cytoskeleton changes and membrane exchange between plasma membrane and endocytic compartments. The presence of ARF6 and its guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) in the brain, as well as its capability to regulate several aspects of neuronal development and synaptic plasticity, has been recently demonstrated. The main purpose of this review is to present the current knowledge about how ARF6 can influence morphological processes crucial for proper formation of the neuronal circuits in the brain, including dendrite and axon differentiation, development of dendritic arbor complexity and dendritic spine formation. Potential effects of ARF6 on synaptic events resulting from its ability to control exo- and endocytosis will be also discussed (c) 2007 Elsevier GmbH. All rights reserved.