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

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

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Abstract Background Neurons assemble into a functional network through a sequence of developmental processes including neuronal polarization and synapse formation.In Caenorhabditis elegans, 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 in vivo.Results We generated a PP1 analog-sensitive variant of SAD-1.Through red label violin strings color code 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.Conclusion 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 porky pig face requirements for SAD-1.