A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation

• Main Authors: Shokat Kevan M, Zhang Chao, Lilley Brendan N, Kim Joanne SM, Sanes Joshua R, Zhen Mei
• Format: Article
• Language: English
• Published: BMC 2008-09-01
• Series: Neural Development
• Online Access: http://www.neuraldevelopment.com/content/3/1/23

<p>Abstract</p> <p>Background</p> <p>Neurons assemble into a functional network through a sequence of developmental processes including neuronal polarization and synapse formation. In <it>Caenorhabditis elegans</it>, the serine/threonine SAD-1 kinase is essential for proper neuronal polarity and synaptic organization. To determine if SAD-1 activity regulates the establishment or maintenance of these neuronal structures, we examined its temporal requirements using a chemical-genetic method that allows for selective and reversible inactivation of its kinase activity <it>in vivo</it>.</p> <p>Results</p> <p>We generated a PP1 analog-sensitive variant of SAD-1. Through temporal inhibition of SAD-1 kinase activity we show that its activity is required for the establishment of both neuronal polarity and synaptic organization. However, while SAD-1 activity is needed strictly when neurons are polarizing, the temporal requirement for SAD-1 is less stringent in synaptic organization, which can also be re-established during maintenance.</p> <p>Conclusion</p> <p>This study reports the first temporal analysis of a neural kinase activity using the chemical-genetic system. It reveals that neuronal polarity and synaptic organization have distinct temporal requirements for SAD-1.</p>