Differential localization and roles of splice variants of rat suppressor of cancer cell invasion (SCAI) in neuronal cells

Miho Mizukoshi, Ayaka Nozawa, Serina Oomizo, Daisuke Ihara, Jun Shiota, Keietsu Kikuchi, Maki Kaito, Yuta Ishibashi, Mitsuru Ishikawa, Mamoru Fukuchi, Masaaki Tsuda, Ichiro Takasaki, Akiko Tabuchi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Suppressor of cancer cell invasion (SCAI) is a suppressor of myocardin-related transcription factor (MRTF)-mediated transcription and cancer cell invasion. However, roles of SCAI in the brain and neuronal cells are not fully resolved. In this study, we initially investigated the distribution of Scai mRNA in the developing rat brain and in neurons. We found that, although Scai mRNA levels decreased during brain development, it was highly expressed in several brain regions and in neurons but not astrocytes. Subsequently, in addition to Scai variant 1, we identified novel rat Scai variants 2 and 3 and characterized their functions in Neuro-2a cells. The novel Scai variants 2 and 3 contain unique exons that possess stop codons and therefore encode shorter proteins compared with the full-length Scai variant 1. SCAI variants 2 and 3 possess a nuclear localization signal, but do not have an MRTF-binding site. Immunostaining of green fluorescent protein (GFP)-tagged SCAI variants revealed a nuclear localization of variant 1, whereas localization of variants 2 and 3 was throughout the cytoplasm and nucleus, suggesting that other nuclear localization signals, which act in Neuro-2a cells, exist in SCAI. All three SCAI variants suppressed the neuron-like morphological change of Neuro-2a cells induced by a Rho effector, constitutively active mDia; however, the suppressive effects of variants 2 and 3 were weaker than that of full-length SCAI variant 1, indicating that the SCAI-mediated change toward a neuronal morphology appeared to be consistent with their nuclear localization. These findings indicate that generation of multiple SCAI splice variants fines-tune neuronal morphology.

Original languageEnglish
Pages (from-to)615-621
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume529
Issue number3
DOIs
StatePublished - 2020/08/27

Keywords

  • Myocardin-related transcription factor (MRTF)
  • Neuronal morphology
  • Splice variant
  • Suppressor of cancer cell invasion (SCAI)
  • mDia

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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