LAMP5 in presynaptic inhibitory terminals in the hindbrain and spinal cord: a role in startle response and auditory processing
LAMP5 in presynaptic inhibitory terminals in the hindbrain and spinal cord: a role in startle response and auditory processing
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DOI：
10.1186/s13041-019-0437-4
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发表时间：
2019-03-12
期刊：
影响因子：
3.6
通讯作者：
Furuichi, Teiichi
中科院分区：
文献类型：
--
作者：
Koebis, Michinori;Urata, Shinji;Furuichi, Teiichi
溶酶体相关膜蛋白5(LAMP5)是秀丽线虫UNC-46蛋白在哺乳动物中的同源蛋白，其功能是将囊泡GABA转运蛋白UNC-47定位于突触小泡。在小鼠前脑中，LAMP5在嗅球和纹状体-黑质系统的GABA能神经元亚群中表达，在那里它是GABA能突触传递的微调所必需的。在这里，我们关注LAMP5在脑干和脊髓中的显著表达，并建议LAMP5在这些脑区发挥作用。LAMP5在耳蜗核、上橄榄复合体、外侧丘系核和脊髓灰质等与听觉加工有关的脑干核团中高表达。正如在前脑中已报道的那样，它仅定位于抑制性突触终末。在缺乏LAMP5的情况下，囊泡抑制性氨基酸转运体(VIAAT)在外侧上橄榄核和耳蜗腹核内的定位没有改变，这表明LAMP5在VIAAT运输中起着保守的作用。Lamp5基因敲除小鼠没有表现出明显的行为异常，但对听觉和触觉刺激的惊吓反应增加。此外，LAMP5缺乏导致听性脑干反应的I、II和V波峰值幅度随强度增加而增大。我们的结果表明，LAMP5在脑干和脊髓的感觉运动处理中起着关键作用。
Lysosome-associated membrane protein 5 (LAMP5) is a mammalian ortholog of the Caenorhabditis elegans protein, UNC-46, which functions as a sorting factor to localize the vesicular GABA transporter UNC-47 to synaptic vesicles. In the mouse forebrain, LAMP5 is expressed in a subpopulation of GABAergic neurons in the olfactory bulb and the striato-nigral system, where it is required for fine-tuning of GABAergic synaptic transmission. Here we focus on the prominent expression of LAMP5 in the brainstem and spinal cord and suggest a role for LAMP5 in these brain regions. LAMP5 was highly expressed in several brainstem nuclei involved with auditory processing including the cochlear nuclei, the superior olivary complex, nuclei of the lateral lemniscus and grey matter in the spinal cord. It was localized exclusively in inhibitory synaptic terminals, as has been reported in the forebrain. In the absence of LAMP5, localization of the vesicular inhibitory amino acid transporter (VIAAT) was unaltered in the lateral superior olive and the ventral cochlear nuclei, arguing against a conserved role for LAMP5 in trafficking VIAAT. Lamp5 knockout mice showed no overt behavioral abnormality but an increased startle response to auditory and tactile stimuli. In addition, LAMP5 deficiency led to a larger intensity-dependent increase of wave I, II and V peak amplitude of auditory brainstem response. Our results indicate that LAMP5 plays a pivotal role in sensorimotor processing in the brainstem and spinal cord.