Synaptic localisation of SRF coactivators, MKL1 and MKL2, and their role in dendritic spine morphology
| Autor: | Yamato Hida, Yuta Ishibashi, Anna Krysiak, Akiko Tabuchi, Hiroyuki Sakagami, Katarzyna Kalita, Mitsuru Ishikawa, Natsumi Satou, Marisa Kaneda, Daisuke Ihara, Mamoru Fukuchi, Toshihisa Ohtsuka |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Dendritic spine Dendritic Spines Science Biology Article Small hairpin RNA 03 medical and health sciences Postsynaptic potential Serum response factor Humans RNA Small Interfering Gene Neurons Multidisciplinary Immunohistochemistry 030104 developmental biology Gene Knockdown Techniques Synapses Synaptic plasticity Trans-Activators Medicine Neuroscience Function (biology) Transcription Factors |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-18905-7 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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