Dynamic subcellular localization and transcription activity of the SRF cofactor MKL2 in the striatum are regulated by MAPK
| Autor: | Mutsuki Amano, Kozo Kaibuchi, Taku Nagai, Yasuhiro Funahashi, Anthony Ariza, Sachi Kozawa, Omar Faruk |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Male Transcriptional Activation Serum Response Factor Xenopus Intracellular Space Medium spiny neuron Biochemistry 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Organ Culture Techniques Cocaine Dopamine Uptake Inhibitors Transcription (biology) Pregnancy Gene expression Serum response factor Chlorocebus aethiops Animals Humans Protein kinase A Transcription factor Mice Inbred ICR Chemistry Corpus Striatum Cell biology Mice Inbred C57BL 030104 developmental biology HEK293 Cells COS Cells Rap1 Female Mitogen-Activated Protein Kinases 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Journal of neurochemistryREFERENCES. 157(6) |
| ISSN: | 1471-4159 |
| Popis: | Dopamine type 1 receptor (D1R) signaling activates protein kinase A (PKA), which then activates mitogen-activated protein kinase (MAPK) through Rap1, in striatal medium spiny neurons (MSNs). MAPK plays a pivotal role in reward-related behavior through the activation of certain transcription factors. How D1R signaling regulates behavior through transcription factors remains largely unknown. CREB-binding protein (CBP) promotes transcription through hundreds of different transcription factors and is also important for reward-related behavior. To identify transcription factors regulated by dopamine signaling in MSNs, we performed a phosphoproteomic analysis using affinity beads coated with CBP. We obtained approximately 40 novel candidate proteins in the striatum of the C57BL/6 mouse brain after cocaine administration. Among them, the megakaryoblastic leukemia-2 (MKL2) protein, a transcriptional coactivator of serum response factor (SRF), was our focus. We found that the interaction between CBP and MKL2 was increased by cocaine administration. Additionally, MKL2, CBP and SRF formed a ternary complex in vivo. The C-terminal domain of MKL2 interacted with CBP-KIX and was phosphorylated by MAPK in COS7 cells. The activation of PKA-MAPK signaling induced the nuclear localization of MKL2 and increased SRF-dependent transcriptional activity in neurons. These results demonstrate that dopamine signaling regulates the interaction of MKL2 with CBP in a phosphorylation-dependent manner and thereby controls SRF-dependent gene expression. Cover Image for this issue: https://doi.org/10.1111/jnc.15067. |
| Databáze: | OpenAIRE |
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