Deletion of the Presynaptic Scaffold CAST Reduces Active Zone Size in Rod Photoreceptors and Impairs Visual Processing
Deletion of the Presynaptic Scaffold CAST Reduces Active Zone Size in Rod Photoreceptors and Impairs Visual Processing
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DOI：
10.1523/jneurosci.0752-12.2012
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发表时间：
2012-08-29
影响因子：
5.3
通讯作者：
Moser, Tobias
中科院分区：
文献类型：
--
作者：
Dieck, Susanne Tom;Specht, Dana;Moser, Tobias
如何在分子水平上调节突触前活动区的大小和形状仍然难以捉摸。在这里，我们通过研究 CAST/ERC2（活性区 (CAZ) 蛋白的细胞基质之一）破坏后的视杆光感受器带状活性区来提供见解。在 CAST 敲除 (CAST(-/-)) 小鼠中，视杆光感受器的数量正常，并且反映其生理群体反应的视网膜电图 (ERG) 的 a 波没有变化。使用免疫荧光和电子显微镜，我们发现视杆突触前活性区的大小、其 Ca2+ 通道补体以及外丛状层的延伸都减小了。此外，我们观察到水平细胞和双极细胞向外核层发芽，表明杆递质释放受损。然而，与 CAZ 蛋白巴松管突变体小鼠不同，CAST(-/-) 小鼠的视杆突触表现出锚定带、正常囊泡密度、簇状 Ca2+ 通道和基本正常的分子组织。视杆活性区尺寸的减小伴随着暗视 ERG 中 b 波幅度的减小。假设基于其他完整的突触结构，剩余释放装置的功能未改变，我们根据我们的发现建议释放速率随活性区域的大小而变化。视网膜神经节细胞的多电极阵列记录显示对比敏感度降低。通过验光也观察到了这一点，此外，验光显示视力下降。我们得出的结论是，CAST 支持大的活动区尺寸和杆带突触的高传输率，这是正常视力所必需的。
How size and shape of presynaptic active zones are regulated at the molecular level has remained elusive. Here we provide insight from studying rod photoreceptor ribbon-type active zones after disruption of CAST/ERC2, one of the cytomatrix of the active zone (CAZ) proteins. Rod photoreceptors were present in normal numbers, and the a-wave of the electroretinogram (ERG)-reflecting their physiological population response-was unchanged in CAST knock-out (CAST(-/-)) mice. Using immunofluorescence and electron microscopy, we found that the size of the rod presynaptic active zones, their Ca2+ channel complement, and the extension of the outer plexiform layer were diminished. Moreover, we observed sprouting of horizontal and bipolar cells toward the outer nuclear layer indicating impaired rod transmitter release. However, rod synapses of CAST(-/-) mice, unlike in mouse mutants for the CAZ protein Bassoon, displayed anchored ribbons, normal vesicle densities, clustered Ca2+ channels, and essentially normal molecular organization. The reduction of the rod active zone size went along with diminished amplitudes of the b-wave in scotopic ERGs. Assuming, based on the otherwise intact synaptic structure, an unaltered function of the remaining release apparatus, we take our finding to suggest a scaling of release rate with the size of the active zone. Multielectrode-array recordings of retinal ganglion cells showed decreased contrast sensitivity. This was also observed by optometry, which, moreover, revealed reduced visual acuity. We conclude that CAST supports large active zone size and high rates of transmission at rod ribbon synapses, which are required for normal vision.