Transmembrane protein 108 is required for glutamatergic transmission in dentate gyrus.

Autor:	Jiao HF; Institute of Life Science, Nanchang University, Nanchang 330031, China.; School of Life Sciences, Nanchang University, Nanchang 330031, China.; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA30912., Sun XD; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA30912., Bates R; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA30912., Xiong L; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA30912., Zhang L; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA30912., Liu F; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA30912., Li L; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA30912., Zhang HS; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA30912., Wang SQ; Institute of Life Science, Nanchang University, Nanchang 330031, China., Xiong MT; Institute of Life Science, Nanchang University, Nanchang 330031, China.; School of Life Sciences, Nanchang University, Nanchang 330031, China., Patel M; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA30912., Stranahan AM; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA30912., Xiong WC; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA30912.; Charlie Norwood Veterans Administration Medical Center, Augusta University, Augusta, GA30912., Li BM; Institute of Life Science, Nanchang University, Nanchang 330031, China; lmei@augusta.edu bmli@ncu.edu.cn.; Jiangxi Medical School, Nanchang University, Nanchang 330031, China., Mei L; Institute of Life Science, Nanchang University, Nanchang 330031, China; lmei@augusta.edu bmli@ncu.edu.cn.; Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA30912.; Charlie Norwood Veterans Administration Medical Center, Augusta University, Augusta, GA30912.; Jiangxi Medical School, Nanchang University, Nanchang 330031, China.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2017 Jan 31; Vol. 114 (5), pp. 1177-1182. Date of Electronic Publication: 2017 Jan 17.
DOI:	10.1073/pnas.1618213114
Abstrakt:	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 neurons were 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. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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