title: Involvement of the serum response factor coactivator megakaryoblastic leukemia (MKL) in the activin-regulated dendritic complexity of rat cortical neurons.
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.
authors: From the Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors: Mitsuru
authors: M
authors: Ishikawa
authors: From the Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors: Naoki
authors: N
authors: Nishijima
authors: From the Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors: Jun
authors: J
authors: Shiota
authors: Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Kanagawa 228-8555, Japan.
authors: Hiroyuki
authors: H
authors: Sakagami
authors: Division for Therapies Against Intractable Diseases, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
authors: Kunihiro
authors: K
authors: Tsuchida
authors: From the Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors: Miho
authors: M
authors: Mizukoshi
authors: From the Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors: Mamoru
authors: M
authors: Fukuchi
authors: From the Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors: Masaaki
authors: M
authors: Tsuda
authors: From the Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Electronic address: atabuchi@pha.u-toyama.ac.jp.
authors: Akiko
authors: A
authors: Tabuchi
mesh_terms: D028341:Activins / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C511173:Mrtfa protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C503315:myocardin-related transcription factor B, mouse; D028341:Activins