Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan.
Department of Otolaryngology, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
Mol Brain. 2019 Mar 12;12(1):20. doi: 10.1186/s13041-019-0437-4.
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.
溶酶体相关膜蛋白 5（LAMP5）是秀丽隐杆线虫蛋白 UNC-46 的哺乳动物同源物，作为分选因子将囊泡 GABA 转运体 UNC-47 定位到突触囊泡。在小鼠前脑中，LAMP5 在嗅球和纹状体-黑质系统中的 GABA 能神经元亚群中表达，在 GABA 能突触传递的微调中起作用。在这里，我们专注于 LAMP5 在脑干和脊髓中的显著表达，并提出 LAMP5 在这些脑区的作用。LAMP5 在参与听觉处理的几个脑干核中高度表达，包括耳蜗核、上橄榄复合体、外侧丘系核和脊髓灰质。它仅定位于抑制性突触末端，如在前脑中所报道的。在缺乏 LAMP5 的情况下，外侧上橄榄核和腹侧耳蜗核中囊泡抑制性氨基酸转运体（VIAAT）的定位没有改变，这表明 LAMP5 在 VIAAT 运输中没有保守作用。Lamp5 敲除小鼠没有明显的行为异常，但对听觉和触觉刺激的惊跳反应增加。此外，LAMP5 缺乏导致听觉脑干反应中 I、II 和 V 波峰幅度的强度依赖性增加更大。我们的结果表明，LAMP5 在脑干和脊髓的感觉运动处理中起关键作用。
