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Neuronal Profilin Isoforms Are Addressed by Different Signalling Pathways

Profilins are prominent regulators of actin dynamics. While most mammalian cells express only one profilin, two isoforms, PFN1 and PFN2a are present in the CNS. To challenge the hypothesis that the expression of two profilin isoforms is linked to the complex shape of neurons and to the activity-depe...

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Autores principales: Murk, Kai, Wittenmayer, Nina, Michaelsen-Preusse, Kristin, Dresbach, Thomas, Schoenenberger, Cora-Ann, Korte, Martin, Jockusch, Brigitte M., Rothkegel, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314592/
https://www.ncbi.nlm.nih.gov/pubmed/22470532
http://dx.doi.org/10.1371/journal.pone.0034167
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author Murk, Kai
Wittenmayer, Nina
Michaelsen-Preusse, Kristin
Dresbach, Thomas
Schoenenberger, Cora-Ann
Korte, Martin
Jockusch, Brigitte M.
Rothkegel, Martin
author_facet Murk, Kai
Wittenmayer, Nina
Michaelsen-Preusse, Kristin
Dresbach, Thomas
Schoenenberger, Cora-Ann
Korte, Martin
Jockusch, Brigitte M.
Rothkegel, Martin
author_sort Murk, Kai
collection PubMed
description Profilins are prominent regulators of actin dynamics. While most mammalian cells express only one profilin, two isoforms, PFN1 and PFN2a are present in the CNS. To challenge the hypothesis that the expression of two profilin isoforms is linked to the complex shape of neurons and to the activity-dependent structural plasticity, we analysed how PFN1 and PFN2a respond to changes of neuronal activity. Simultaneous labelling of rodent embryonic neurons with isoform-specific monoclonal antibodies revealed both isoforms in the same synapse. Immunoelectron microscopy on brain sections demonstrated both profilins in synapses of the mature rodent cortex, hippocampus and cerebellum. Both isoforms were significantly more abundant in postsynaptic than in presynaptic structures. Immunofluorescence showed PFN2a associated with gephyrin clusters of the postsynaptic active zone in inhibitory synapses of embryonic neurons. When cultures were stimulated in order to change their activity level, active synapses that were identified by the uptake of synaptotagmin antibodies, displayed significantly higher amounts of both isoforms than non-stimulated controls. Specific inhibition of NMDA receptors by the antagonist APV in cultured rat hippocampal neurons resulted in a decrease of PFN2a but left PFN1 unaffected. Stimulation by the brain derived neurotrophic factor (BDNF), on the other hand, led to a significant increase in both synaptic PFN1 and PFN2a. Analogous results were obtained for neuronal nuclei: both isoforms were localized in the same nucleus, and their levels rose significantly in response to KCl stimulation, whereas BDNF caused here a higher increase in PFN1 than in PFN2a. Our results strongly support the notion of an isoform specific role for profilins as regulators of actin dynamics in different signalling pathways, in excitatory as well as in inhibitory synapses. Furthermore, they suggest a functional role for both profilins in neuronal nuclei.
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spelling pubmed-33145922012-04-02 Neuronal Profilin Isoforms Are Addressed by Different Signalling Pathways Murk, Kai Wittenmayer, Nina Michaelsen-Preusse, Kristin Dresbach, Thomas Schoenenberger, Cora-Ann Korte, Martin Jockusch, Brigitte M. Rothkegel, Martin PLoS One Research Article Profilins are prominent regulators of actin dynamics. While most mammalian cells express only one profilin, two isoforms, PFN1 and PFN2a are present in the CNS. To challenge the hypothesis that the expression of two profilin isoforms is linked to the complex shape of neurons and to the activity-dependent structural plasticity, we analysed how PFN1 and PFN2a respond to changes of neuronal activity. Simultaneous labelling of rodent embryonic neurons with isoform-specific monoclonal antibodies revealed both isoforms in the same synapse. Immunoelectron microscopy on brain sections demonstrated both profilins in synapses of the mature rodent cortex, hippocampus and cerebellum. Both isoforms were significantly more abundant in postsynaptic than in presynaptic structures. Immunofluorescence showed PFN2a associated with gephyrin clusters of the postsynaptic active zone in inhibitory synapses of embryonic neurons. When cultures were stimulated in order to change their activity level, active synapses that were identified by the uptake of synaptotagmin antibodies, displayed significantly higher amounts of both isoforms than non-stimulated controls. Specific inhibition of NMDA receptors by the antagonist APV in cultured rat hippocampal neurons resulted in a decrease of PFN2a but left PFN1 unaffected. Stimulation by the brain derived neurotrophic factor (BDNF), on the other hand, led to a significant increase in both synaptic PFN1 and PFN2a. Analogous results were obtained for neuronal nuclei: both isoforms were localized in the same nucleus, and their levels rose significantly in response to KCl stimulation, whereas BDNF caused here a higher increase in PFN1 than in PFN2a. Our results strongly support the notion of an isoform specific role for profilins as regulators of actin dynamics in different signalling pathways, in excitatory as well as in inhibitory synapses. Furthermore, they suggest a functional role for both profilins in neuronal nuclei. Public Library of Science 2012-03-28 /pmc/articles/PMC3314592/ /pubmed/22470532 http://dx.doi.org/10.1371/journal.pone.0034167 Text en Murk et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Murk, Kai
Wittenmayer, Nina
Michaelsen-Preusse, Kristin
Dresbach, Thomas
Schoenenberger, Cora-Ann
Korte, Martin
Jockusch, Brigitte M.
Rothkegel, Martin
Neuronal Profilin Isoforms Are Addressed by Different Signalling Pathways
title Neuronal Profilin Isoforms Are Addressed by Different Signalling Pathways
title_full Neuronal Profilin Isoforms Are Addressed by Different Signalling Pathways
title_fullStr Neuronal Profilin Isoforms Are Addressed by Different Signalling Pathways
title_full_unstemmed Neuronal Profilin Isoforms Are Addressed by Different Signalling Pathways
title_short Neuronal Profilin Isoforms Are Addressed by Different Signalling Pathways
title_sort neuronal profilin isoforms are addressed by different signalling pathways
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314592/
https://www.ncbi.nlm.nih.gov/pubmed/22470532
http://dx.doi.org/10.1371/journal.pone.0034167
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