State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China.
Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou 325000, China
eNeuro. 2024 Sep 23;11(9). doi: 10.1523/ENEURO.0145-24.2024. Print 2024 Sep.
Ca-binding proteins (CaBPs; CaBP1-5) are a subfamily of neuronal Ca sensors with high homology to calmodulin. Notably, CaBP4, which is exclusively expressed in rod and cone photoreceptors, is crucial for maintaining normal retinal functions. However, the functional roles of CaBP1, CaBP2, and CaBP5 in the retina remain elusive, primarily due to limited understanding of their expression patterns within inner retinal neurons. In this study, we conducted a comprehensive transcript analysis using single-cell RNA sequencing datasets to investigate the gene expression profiles of CaBPs in mouse and human retinal neurons. Our findings revealed notable similarities in the overall expression patterns of CaBPs across both species. Specifically, nearly all amacrine cell, ganglion cell, and horizontal cell types exclusively expressed CaBP1. In contrast, the majority of bipolar cell types, including rod bipolar (RB) cells, expressed distinct combinations of CaBP1, CaBP2, and CaBP5, rather than a single CaBP as previously hypothesized. Remarkably, mouse rods and human cones exclusively expressed CaBP4, whereas mouse cones and human rods coexpressed both CaBP4 and CaBP5. Our single-cell reverse transcription polymerase chain reaction analysis confirmed the coexpression CaBP1 and CaBP5 in individual RBs from mice of either sex. Additionally, all three splice variants of CaBP1, primarily L-CaBP1, were detected in mouse RBs. Taken together, our study offers a comprehensive overview of the distribution of CaBPs in mouse and human retinal neurons, providing valuable insights into their roles in visual functions.
钙结合蛋白（CaBPs；CaBP1-5）是神经元钙传感器的一个亚家族，与钙调蛋白具有高度同源性。值得注意的是，仅在视杆和视锥光感受器中表达的 CaBP4 对于维持正常的视网膜功能至关重要。然而，CaBP1、CaBP2 和 CaBP5 在视网膜中的功能作用仍然难以捉摸，主要是因为对它们在内视网膜神经元中的表达模式的理解有限。在这项研究中，我们使用单细胞 RNA 测序数据集进行了全面的转录分析，以研究 CaBP 在小鼠和人视网膜神经元中的基因表达谱。我们的研究结果表明，CaBP 在这两个物种中的总体表达模式具有显著的相似性。具体而言，几乎所有的无长突细胞、节细胞和水平细胞类型都仅表达 CaBP1。相比之下，大多数双极细胞类型，包括视杆双极（RB）细胞，表达的 CaBP1、CaBP2 和 CaBP5 组合与之前假设的单一 CaBP 不同。值得注意的是，小鼠视杆细胞和人视锥细胞仅表达 CaBP4，而小鼠视锥细胞和人视杆细胞共同表达 CaBP4 和 CaBP5。我们的单细胞逆转录聚合酶链反应分析证实了来自雌雄小鼠的单个 RB 中 CaBP1 和 CaBP5 的共表达。此外，还检测到了 CaBP1 的所有三种剪接变体，主要是 L-CaBP1，存在于小鼠的 RB 中。综上所述，我们的研究提供了 CaBP 在小鼠和人视网膜神经元中的分布的全面概述，为它们在视觉功能中的作用提供了有价值的见解。
