Synaptic localisation of SRF coactivators, MKL1 and MKL2, and their role in dendritic spine morphology

Abstract The megakaryoblastic leukaemia (MKL) family are serum response factor (SRF) coactivators, which are highly expressed in the brain. Accordingly, MKL plays important roles in dendritic morphology, neuronal migration, and brain development. Further, nucleotide substitutions in the MKL1 and MKL...

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Autores principales:	Marisa Kaneda, Hiroyuki Sakagami, Yamato Hida, Toshihisa Ohtsuka, Natsumi Satou, Yuta Ishibashi, Mamoru Fukuchi, Anna Krysiak, Mitsuru Ishikawa, Daisuke Ihara, Katarzyna Kalita, Akiko Tabuchi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/88d1491198894e9e8bae2c3933ed5fc8
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spelling	oai:doaj.org-article:88d1491198894e9e8bae2c3933ed5fc82021-12-02T15:08:23ZSynaptic localisation of SRF coactivators, MKL1 and MKL2, and their role in dendritic spine morphology10.1038/s41598-017-18905-72045-2322https://doaj.org/article/88d1491198894e9e8bae2c3933ed5fc82018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-18905-7https://doaj.org/toc/2045-2322Abstract The megakaryoblastic leukaemia (MKL) family are serum response factor (SRF) coactivators, which are highly expressed in the brain. Accordingly, MKL plays important roles in dendritic morphology, neuronal migration, and brain development. Further, nucleotide substitutions in the MKL1 and MKL2 genes are found in patients with schizophrenia and autism spectrum disorder, respectively. Thus, studies on the precise synaptic localisation and function of MKL in neurons are warranted. In this study, we generated and tested new antibodies that specifically recognise endogenously expressed MKL1 and MKL2 proteins in neurons. Using these reagents, we biochemically and immunocytochemically show that MKL1 and MKL2 are localised at synapses. Furthermore, shRNA experiments revealed that postsynaptic deletion of MKL1 or MKL2 reduced the percentage of mushroom- or stubby-type spines in cultured neurons. Taken together, our findings suggest that MKL1 and MKL2 are present at synapses and involved in dendritic spine maturation. This study may, at least in part, contribute to better understanding of the molecular mechanisms underlying MKL-mediated synaptic plasticity and neurological disorders.Marisa KanedaHiroyuki SakagamiYamato HidaToshihisa OhtsukaNatsumi SatouYuta IshibashiMamoru FukuchiAnna KrysiakMitsuru IshikawaDaisuke IharaKatarzyna KalitaAkiko TabuchiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marisa Kaneda Hiroyuki Sakagami Yamato Hida Toshihisa Ohtsuka Natsumi Satou Yuta Ishibashi Mamoru Fukuchi Anna Krysiak Mitsuru Ishikawa Daisuke Ihara Katarzyna Kalita Akiko Tabuchi Synaptic localisation of SRF coactivators, MKL1 and MKL2, and their role in dendritic spine morphology
description	Abstract The megakaryoblastic leukaemia (MKL) family are serum response factor (SRF) coactivators, which are highly expressed in the brain. Accordingly, MKL plays important roles in dendritic morphology, neuronal migration, and brain development. Further, nucleotide substitutions in the MKL1 and MKL2 genes are found in patients with schizophrenia and autism spectrum disorder, respectively. Thus, studies on the precise synaptic localisation and function of MKL in neurons are warranted. In this study, we generated and tested new antibodies that specifically recognise endogenously expressed MKL1 and MKL2 proteins in neurons. Using these reagents, we biochemically and immunocytochemically show that MKL1 and MKL2 are localised at synapses. Furthermore, shRNA experiments revealed that postsynaptic deletion of MKL1 or MKL2 reduced the percentage of mushroom- or stubby-type spines in cultured neurons. Taken together, our findings suggest that MKL1 and MKL2 are present at synapses and involved in dendritic spine maturation. This study may, at least in part, contribute to better understanding of the molecular mechanisms underlying MKL-mediated synaptic plasticity and neurological disorders.
format	article
author	Marisa Kaneda Hiroyuki Sakagami Yamato Hida Toshihisa Ohtsuka Natsumi Satou Yuta Ishibashi Mamoru Fukuchi Anna Krysiak Mitsuru Ishikawa Daisuke Ihara Katarzyna Kalita Akiko Tabuchi
author_facet	Marisa Kaneda Hiroyuki Sakagami Yamato Hida Toshihisa Ohtsuka Natsumi Satou Yuta Ishibashi Mamoru Fukuchi Anna Krysiak Mitsuru Ishikawa Daisuke Ihara Katarzyna Kalita Akiko Tabuchi
author_sort	Marisa Kaneda
title	Synaptic localisation of SRF coactivators, MKL1 and MKL2, and their role in dendritic spine morphology
title_short	Synaptic localisation of SRF coactivators, MKL1 and MKL2, and their role in dendritic spine morphology
title_full	Synaptic localisation of SRF coactivators, MKL1 and MKL2, and their role in dendritic spine morphology
title_fullStr	Synaptic localisation of SRF coactivators, MKL1 and MKL2, and their role in dendritic spine morphology
title_full_unstemmed	Synaptic localisation of SRF coactivators, MKL1 and MKL2, and their role in dendritic spine morphology
title_sort	synaptic localisation of srf coactivators, mkl1 and mkl2, and their role in dendritic spine morphology
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/88d1491198894e9e8bae2c3933ed5fc8
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Synaptic localisation of SRF coactivators, MKL1 and MKL2, and their role in dendritic spine morphology

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