Switch-like PKA responses in the nucleus of striatal neurons.

Autor:	Yapo C; Sorbonne Université, CNRS, Biological Adaptation and Ageing, F-75005 Paris, France., Nair AG; Science for Life Laboratory, School of Computer Science and Communication, KTH Royal Institute of Technology, Stockholm, 10044, Sweden.; National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India.; Manipal University, Manipal 576104, India., Hellgren Kotaleski J; Science for Life Laboratory, School of Computer Science and Communication, KTH Royal Institute of Technology, Stockholm, 10044, Sweden.; Department of Neuroscience, Karolinska Institutet, Solna, 17177, Sweden., Vincent P; Sorbonne Université, CNRS, Biological Adaptation and Ageing, F-75005 Paris, France pierre.vincent@upmc.fr., Castro LRV; Sorbonne Université, CNRS, Biological Adaptation and Ageing, F-75005 Paris, France.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2018 Jul 27; Vol. 131 (14). Date of Electronic Publication: 2018 Jul 27.
DOI:	10.1242/jcs.216556
Abstrakt:	Although it is known that protein kinase A (PKA) in the nucleus regulates gene expression, the specificities of nuclear PKA signaling remain poorly understood. Here, we combined computational modeling and live-cell imaging of PKA-dependent phosphorylation in mouse brain slices to investigate how transient dopamine signals are translated into nuclear PKA activity in cortical pyramidal neurons and striatal medium spiny neurons. We observed that the nuclear PKA signal in striatal neurons featured an ultrasensitive responsiveness, associated with fast all-or-none responses, which is not consistent with the commonly accepted theory of a slow and passive diffusion of catalytic PKA in the nucleus. Our numerical model suggests that a positive feed-forward mechanism inhibiting nuclear phosphatase activity - possibly mediated by DARPP-32 (also known as PPP1R1B) - could be responsible for this non-linear pattern of nuclear PKA response, allowing for a better detection of the transient dopamine signals that are often associated with reward-mediated learning. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2018. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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