Svetlana Smith-Trunova1, Ranjini Prithviraj1, Joshua Spurrier1,2, Irina Kuzina1, Qun Gu1, Edward Giniger1. 1. National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. 2. The Johns Hopkins University/National Institutes of Health Graduate Partnership Program, National Institutes of Health, Bethesda, Maryland.
Abstract
BACKGROUND: During metamorphosis, axons and dendrites of the mushroom body (MB) in the Drosophila central brain are remodeled extensively to support the transition from larval to adult behaviors. RESULTS: We show here that the neuronal cyclin-dependent kinase, Cdk5, regulates the timing and rate of mushroom body remodeling: reduced Cdk5 activity causes a delay in pruning of MB neurites, while hyperactivation accelerates it. We further show that Cdk5 cooperates with the ubiquitin-proteasome system in this process. Finally, we show that Cdk5 modulates the first overt step in neurite disassembly, dissolution of the neuronal tubulin cytoskeleton, and provide evidence that it also acts at additional steps of MB pruning. CONCLUSIONS: These data show that Cdk5 regulates the onset and extent of remodeling of the Drosophila MB. Given the wide phylogenetic conservation of Cdk5, we suggest that it is likely to play a role in developmental remodeling in other systems, as well. Moreover, we speculate that the well-established role of Cdk5 in neurodegeneration may involve some of the same cellular mechanisms that it uses during developmental remodeling. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
BACKGROUND: During metamorphosis, axons and dendrites of the mushroom body (MB) in the Drosophila central brain are remodeled extensively to support the transition from larval to adult behaviors. RESULTS: We show here that the neuronal cyclin-dependent kinase, Cdk5, regulates the timing and rate of mushroom body remodeling: reduced Cdk5 activity causes a delay in pruning of MB neurites, while hyperactivation accelerates it. We further show that Cdk5 cooperates with the ubiquitin-proteasome system in this process. Finally, we show that Cdk5 modulates the first overt step in neurite disassembly, dissolution of the neuronal tubulin cytoskeleton, and provide evidence that it also acts at additional steps of MB pruning. CONCLUSIONS: These data show that Cdk5 regulates the onset and extent of remodeling of the Drosophila MB. Given the wide phylogenetic conservation of Cdk5, we suggest that it is likely to play a role in developmental remodeling in other systems, as well. Moreover, we speculate that the well-established role of Cdk5 in neurodegeneration may involve some of the same cellular mechanisms that it uses during developmental remodeling. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Authors: Eric D Hoopfer; Todd McLaughlin; Ryan J Watts; Oren Schuldiner; Dennis D M O'Leary; Liqun Luo Journal: Neuron Date: 2006-06-15 Impact factor: 17.173