Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1782159812667113472 |
---|---|
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. |
format | Text |
id | pubmed-2564922 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT kimjoannesm achemicalgeneticstrategyrevealsdistincttemporalrequirementsforsad1kinaseinneuronalpolarizationandsynapseformation AT lilleybrendann achemicalgeneticstrategyrevealsdistincttemporalrequirementsforsad1kinaseinneuronalpolarizationandsynapseformation AT zhangchao achemicalgeneticstrategyrevealsdistincttemporalrequirementsforsad1kinaseinneuronalpolarizationandsynapseformation AT shokatkevanm achemicalgeneticstrategyrevealsdistincttemporalrequirementsforsad1kinaseinneuronalpolarizationandsynapseformation AT sanesjoshuar achemicalgeneticstrategyrevealsdistincttemporalrequirementsforsad1kinaseinneuronalpolarizationandsynapseformation AT zhenmei achemicalgeneticstrategyrevealsdistincttemporalrequirementsforsad1kinaseinneuronalpolarizationandsynapseformation AT kimjoannesm chemicalgeneticstrategyrevealsdistincttemporalrequirementsforsad1kinaseinneuronalpolarizationandsynapseformation AT lilleybrendann chemicalgeneticstrategyrevealsdistincttemporalrequirementsforsad1kinaseinneuronalpolarizationandsynapseformation AT zhangchao chemicalgeneticstrategyrevealsdistincttemporalrequirementsforsad1kinaseinneuronalpolarizationandsynapseformation AT shokatkevanm chemicalgeneticstrategyrevealsdistincttemporalrequirementsforsad1kinaseinneuronalpolarizationandsynapseformation AT sanesjoshuar chemicalgeneticstrategyrevealsdistincttemporalrequirementsforsad1kinaseinneuronalpolarizationandsynapseformation AT zhenmei chemicalgeneticstrategyrevealsdistincttemporalrequirementsforsad1kinaseinneuronalpolarizationandsynapseformation |