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

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 i...

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Autores principales: Kim, Joanne SM, Lilley, Brendan N, Zhang, Chao, Shokat, Kevan M, Sanes, Joshua R, Zhen, Mei
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2564922/
https://www.ncbi.nlm.nih.gov/pubmed/18808695
http://dx.doi.org/10.1186/1749-8104-3-23
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author Kim, Joanne SM
Lilley, Brendan N
Zhang, Chao
Shokat, Kevan M
Sanes, Joshua R
Zhen, Mei
author_facet Kim, Joanne SM
Lilley, Brendan N
Zhang, Chao
Shokat, Kevan M
Sanes, Joshua R
Zhen, Mei
author_sort Kim, Joanne SM
collection PubMed
description 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 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 requirements for SAD-1.
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spelling pubmed-25649222008-10-09 A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation Kim, Joanne SM Lilley, Brendan N Zhang, Chao Shokat, Kevan M Sanes, Joshua R Zhen, Mei Neural Develop Research Article 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 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 requirements for SAD-1. BioMed Central 2008-09-22 /pmc/articles/PMC2564922/ /pubmed/18808695 http://dx.doi.org/10.1186/1749-8104-3-23 Text en Copyright © 2008 Kim et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kim, Joanne SM
Lilley, Brendan N
Zhang, Chao
Shokat, Kevan M
Sanes, Joshua R
Zhen, Mei
A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation
title A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation
title_full A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation
title_fullStr A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation
title_full_unstemmed A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation
title_short A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation
title_sort chemical-genetic strategy reveals distinct temporal requirements for sad-1 kinase in neuronal polarization and synapse formation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2564922/
https://www.ncbi.nlm.nih.gov/pubmed/18808695
http://dx.doi.org/10.1186/1749-8104-3-23
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