Neuronal profilin isoforms are addressed by different signalling pathways

Murk, Kai and Wittenmayer, Nina and Michaelsen-Preusse, Kristin and Dresbach, Thomas and Schoenenberger, Cora-Ann and Korte, Martin and Jockusch, Brigitte M. and Rothkegel, Martin. (2012) Neuronal profilin isoforms are addressed by different signalling pathways. PLoS ONE, Vol. 7, H. 3 , e34167.

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Official URL: http://edoc.unibas.ch/dok/A6043728

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Structural Biology (Schoenenberger)
UniBasel Contributors:Schoenenberger, Cora-Ann
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Aug 2018 06:39
Deposited On:01 Feb 2013 08:39

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