Leucine-rich glioma inactivated 1 (Lgi1), an epilepsy-related secreted protein, has a nuclear localization signal and localizes to both the cytoplasm and the nucleus of the caudal ganglionic eminence neurons

Sayaka Kusuzawa, Takao Honda, Yuko Fukata, Masaki Fukata, Shigeaki Kanatani, Daisuke H. Tanaka, Kazunori Nakajima

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Leucine-rich glioma inactivated 1 (Lgi1) is a secreted synaptic protein that organizes a transsynaptic protein complex throughout the brain. Mutations in the Lgi1 gene have been found in patients with autosomal dominant lateral temporal lobe epilepsy (ADLTE). Although a large number of studies have focused on the expression and function of Lgi1 in the postnatal brain, information regarding its functions and distribution during development remains sparse. Here we report that Lgi1 mRNA is preferentially expressed in the caudal ganglionic eminence (CGE) of the early embryonic telencephalon, and LGI1 protein is unexpectedly localized in the nucleus of dissociated CGE neurons. Using bioinformatics analysis, we found that LGI1 contains a putative nuclear localization signal (NLS) in its leucine-rich repeat C-terminal domain. Furthermore, we show that the transient expression of Lgi1 in CGE neurons resulted in nuclear translocation of the LGI1 protein, and a mutation in the NLS led to the retention of LGI1 in the cytoplasm. We also confirmed that the NLS sequence of LGI1 had the ability to mediate the nuclear localization by using the NLS-containing fusion protein. Interestingly, when Lgi1 was expressed in neurons obtained from the medial ganglionic eminence or cerebral cortex, almost no nuclear localization of LGI1 was observed. These results raise the possibility of a novel role of Lgi1 within embryonic neurons through nuclear translocation and may provide insight into its potential effects on the development of the central nervous system and ADLTE pathogenesis. Lgi1 mRNA is preferentially expressed in the caudal ganglionic eminence and cortical cells of the early embryonic telencephalon. LGI1 protein is unexpectedly localized in the nucleus only within the dissociated CGE neurons. We have also confirmed that the NLS sequence of LGI1 had the ability to mediate the nuclear localization. Our findings raised the possibility of a novel role of Lgi1 within embryonic neurons through nuclear translocation.

Original languageEnglish
Pages (from-to)2284-2292
Number of pages9
JournalEuropean Journal of Neuroscience
Volume36
Issue number3
DOIs
Publication statusPublished - 2012 Aug

Fingerprint

Nuclear Localization Signals
Leucine
Glioma
Epilepsy
Cytoplasm
Neurons
Proteins
Telencephalon
Protein Sorting Signals
Messenger RNA
Median Eminence
Mutation
Terminal Repeat Sequences
Brain
Protein Transport
Computational Biology
Cerebral Cortex
Central Nervous System

Keywords

  • Autosomal dominant lateral temporal lobe epilepsy
  • Caudal ganglionic eminence
  • Cortical development
  • Leucine-rich repeat
  • Mouse
  • Nuclear localization

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Leucine-rich glioma inactivated 1 (Lgi1), an epilepsy-related secreted protein, has a nuclear localization signal and localizes to both the cytoplasm and the nucleus of the caudal ganglionic eminence neurons. / Kusuzawa, Sayaka; Honda, Takao; Fukata, Yuko; Fukata, Masaki; Kanatani, Shigeaki; Tanaka, Daisuke H.; Nakajima, Kazunori.

In: European Journal of Neuroscience, Vol. 36, No. 3, 08.2012, p. 2284-2292.

Research output: Contribution to journalArticle

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abstract = "Leucine-rich glioma inactivated 1 (Lgi1) is a secreted synaptic protein that organizes a transsynaptic protein complex throughout the brain. Mutations in the Lgi1 gene have been found in patients with autosomal dominant lateral temporal lobe epilepsy (ADLTE). Although a large number of studies have focused on the expression and function of Lgi1 in the postnatal brain, information regarding its functions and distribution during development remains sparse. Here we report that Lgi1 mRNA is preferentially expressed in the caudal ganglionic eminence (CGE) of the early embryonic telencephalon, and LGI1 protein is unexpectedly localized in the nucleus of dissociated CGE neurons. Using bioinformatics analysis, we found that LGI1 contains a putative nuclear localization signal (NLS) in its leucine-rich repeat C-terminal domain. Furthermore, we show that the transient expression of Lgi1 in CGE neurons resulted in nuclear translocation of the LGI1 protein, and a mutation in the NLS led to the retention of LGI1 in the cytoplasm. We also confirmed that the NLS sequence of LGI1 had the ability to mediate the nuclear localization by using the NLS-containing fusion protein. Interestingly, when Lgi1 was expressed in neurons obtained from the medial ganglionic eminence or cerebral cortex, almost no nuclear localization of LGI1 was observed. These results raise the possibility of a novel role of Lgi1 within embryonic neurons through nuclear translocation and may provide insight into its potential effects on the development of the central nervous system and ADLTE pathogenesis. Lgi1 mRNA is preferentially expressed in the caudal ganglionic eminence and cortical cells of the early embryonic telencephalon. LGI1 protein is unexpectedly localized in the nucleus only within the dissociated CGE neurons. We have also confirmed that the NLS sequence of LGI1 had the ability to mediate the nuclear localization. Our findings raised the possibility of a novel role of Lgi1 within embryonic neurons through nuclear translocation.",
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