Elsevier

Neuroscience

Volume 158, Issue 2, 23 January 2009, Pages 369-372
Neuroscience

Rapid Report
Phosphorylation of ΔFosB mediates its stability in vivo

https://doi.org/10.1016/j.neuroscience.2008.10.059Get rights and content

Abstract

The transcription factor, ΔFosB, accumulates in a region-specific manner in brain in response to many types of chronic stimulation due to the unusual stability of the protein. The phosphorylation of Ser27 in ΔFosB has been shown to promote this stability in vitro. We show here that this phosphorylation reaction is also important for ΔFosB's stability in the brain in vivo and for the unique behavioral plasticity mediated by this transcription factor.

Section snippets

Experimental procedures

To study the effect of Ser27 phosphorylation on the stability of ΔFosB within the brain in vivo, we generated herpes simplex virus (HSV) vectors encoding either wild-type ΔFosB (HSV-ΔFosB) or altered forms of ΔFosB with Ser to Ala [HSV-ΔFosB(Ser27Ala)] or Ser to Glu [HSV-ΔFosB(Ser27Glu)] mutations. The Ser to Ala mutation obliterates Ser27 phosphorylation, whereas the Ser to Glu mutation is a “phosphomimetic” alteration in that the negatively charged Glu residue can mimic a phospho-Ser residue

Results

The question we first addressed was: Does mutation of Ser27 with Ala or Glu alter the persistence of ΔFosB in brain? As shown in Fig. 1, all three vectors induced roughly comparable levels of ΔFosB protein within the site of the injection as evaluated on day 3, when levels of transgene expression are still at maximal levels. By days 6–14, levels of ΔFosB expression decayed appreciably in all three groups. However, at these later time points, clear differences were observed in persisting

Discussion

The persistent expression of ΔFosB in the nucleus accumbens has been shown to be a crucial mechanism underlying sensitized responses to cocaine and other drugs of abuse (Kelz et al 1999, Colby et al 2003; McClung et al 2004, Zachariou et al 2006) as well as to natural rewards such as wheel running (Werme et al., 2002), food (Olausson et al 2006, Wallace et al 2008), and sex (Wallace et al., 2008). This persistent expression has been shown to correlate in previous studies with the enhanced

Acknowledgments

This work was supported by grants from the National Institute on Drug Abuse and National Institute of Mental Health.

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