Involvement of the serum response factor coactivator megakaryoblastic leukemia (MKL) in the activin-regulated dendritic complexity of rat cortical neurons

Mitsuru Ishikawa, Naoki Nishijima, Jun Shiota, Hiroyuki Sakagami, Kunihiro Tsuchida, Miho Mizukoshi, Mamoru Fukuchi, Masaaki Tsuda, Akiko Tabuchi

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Abstract

Dynamic changes in neuronal morphology and transcriptional regulation play crucial roles in the neuronal network and function. Accumulating evidence suggests that the megakaryoblastic leukemia (MKL) family members, which function not only as actin-binding proteins but also as serum response factor (SRF) transcriptional coactivators, regulate neuronal morphology. However, the extracellular ligands and signaling pathways, which activate MKL-mediated morphological changes in neurons, remain unresolved. Here, we demonstrate that in addition to MKL1, MKL2, highly enriched in the forebrain, strongly contributes to the dendritic complexity, and this process is triggered by stimulation with activin, a member of the transforming growth factor β (TGF-β) superfamily. Activin promoted dendritic complexity in a SRF- and MKL-dependent manner without drastically affecting MKL localization and protein levels. In contrast, activin promoted the nuclear export of suppressor of cancer cell invasion (SCAI), which is a corepressor for SRF and MKL. Furthermore, overexpression of SCAI blocked activin-induced SRF transcriptional responses and dendritic complexity. Collectively, these results strongly suggest that activin-SCAI-MKL signaling is a novel pathway that regulates the dendritic morphology of rat cortical neurons by excluding SCAI from the nucleus and activating MKL/SRF-mediated gene expression.

Original languageEnglish
Pages (from-to)32734-32743
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number43
DOIs
Publication statusPublished - 22-10-2010

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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