Transmembrane protein 108 is required for glutamatergic transmission in dentate gyrus

Hui Feng Jiao, Xiang Dong Sun, Ryan Bates, Lei Xiong, Lei Zhang, Fang Liu, Lei Li, Hong Sheng Zhang, Shun Qi Wang, Ming Tao Xiong, Mihir Patel, Alexis Michelle Stranahan, Wencheng Xiong, Bao Ming Li, Lin Mei

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Neurotransmission in dentate gyrus (DG) is critical for spatial coding, learning memory, and emotion processing. Although DG dysfunction is implicated in psychiatric disorders, including schizophrenia, underlying pathological mechanisms remain unclear. Here we report that transmembrane protein 108 (Tmem108), a novel schizophrenia susceptibility gene, is highly enriched in DG granule neurons and its expression increased at the postnatal period critical for DG development. Tmem108 is specifically expressed in the nervous system and enriched in the postsynaptic density fraction. Tmem108-deficient neurons form fewer and smaller spines, suggesting that Tmem108 is required for spine formation and maturation. In agreement, excitatory postsynaptic currents of DG granule neuronswere decreased in Tmem108 mutant mice, indicating a hypofunction of glutamatergic activity. Further cell biological studies indicate that Tmem108 is necessary for surface expression of AMPA receptors. Tmem108-deficient mice display compromised sensorimotor gating and cognitive function. Together, these observations indicate that Tmem108 plays a critical role in regulating spine development and excitatory transmission in DG granule neurons. When Tmem108 is mutated, mice displayed excitatory/inhibitory imbalance and behavioral deficits relevant to schizophrenia, revealing potential pathophysiological mechanisms of schizophrenia.

Original languageEnglish (US)
Pages (from-to)1177-1182
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number5
DOIs
StatePublished - Jan 31 2017

Keywords

  • AMPA receptors
  • Dentate gyrus
  • Glutamatergic transmission
  • Schizophrenia
  • Spine

ASJC Scopus subject areas

  • General

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