Immunocytochemical evidence of Tulp1-dependent outer segment protein transport pathways in photoreceptor cells.
Immunocytochemical evidence of Tulp1-dependent outer segment protein transport pathways in photoreceptor cells.
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光感受器细胞中依赖TULP1的外部段蛋白转运途径的免疫细胞化学证据。
DOI：
10.1016/j.exer.2011.08.005
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发表时间：
2011-11
影响因子：
3.4
通讯作者：
Hagstrom, Stephanie A.
中科院分区：
文献类型：
--
作者：
Grossman, Gregory H.;Watson, Rao F.;Pauer, Gayle J. T.;Bollinger, Kathryn;Hagstrom, Stephanie A.
关键词：
Tulp 1是一种功能未知的蛋白质，只存在于视杆细胞和视锥细胞中。该基因突变导致人类常染色体隐性视网膜色素变性和小鼠感光细胞变性。在tulp 1 −/−小鼠中，视杆细胞和视锥细胞视蛋白被错误定位，带有视紫红质的细胞外囊泡在内节周围积聚，表明Tulp 1参与了从内节到外节的蛋白质转运。为了进一步研究这一点，我们试图确定哪些外节转运途径是Tulp 1依赖的。我们使用免疫组织化学来检查视网膜变性前tulp 1 −/−光感受器外节蛋白的定位。并对内节细胞器和视紫红质转运机制蛋白进行了研究。在此，我们表明，鸟苷酸环化酶1和鸟苷酸环化酶激活蛋白1和2是错误定位在Tulp 1的情况下。此外，arrestin不会响应于光刺激而移位到外节。此外，来自tulp 1 −/−视网膜的数据增加了对外周膜蛋白转运的理解，表明视紫红质激酶和转导蛋白在视紫红质载体囊泡中不共转运，磷酸二酯酶在鸟苷酸环化酶载体囊泡中不共转运。这些数据表明Tulp 1参与了选择性整合膜外段蛋白及其相关蛋白的转运，特别是视蛋白和鸟苷酸环化酶载体途径。Tulp 1在外节蛋白转运中的确切作用仍然难以捉摸。然而，没有Tulp 1，两个视紫红质转运机制蛋白表现出异常分布，Rab 8和Rab 11，这表明Tulp 1在连接纤毛附近的质膜上的囊泡对接和融合中的作用。
Tulp1 is a protein of unknown function exclusive to rod and cone photoreceptor cells. Mutations in the gene cause autosomal recessive retinitis pigmentosa in humans and photoreceptor degeneration in mice. In tulp1−/− mice, rod and cone opsins are mislocalized, and rhodopsin-bearing extracellular vesicles accumulate around the inner segment, indicating that Tulp1 is involved in protein transport from the inner segment to the outer segment. To investigate this further, we sought to define which outer segment transport pathways are Tulp1-dependent. We used immunohistochemistry to examine the localization of outer segment proteins in tulp1−/− photoreceptors, prior to retinal degeneration. We also surveyed the condition of inner segment organelles and rhodopsin transport machinery proteins. Herein, we show that guanylate cyclase 1 and guanylate cyclase activating proteins 1 and 2 are mislocalized in the absence of Tulp1. Furthermore, arrestin does not translocate to the outer segment in response to light stimulation. Additionally, data from the tulp1−/− retina adds to the understanding of peripheral membrane protein transport, indicating that rhodopsin kinase and transducin do not co-transport in rhodopsin carrier vesicles and phosphodiesterase does not co-transport in guanylate cyclase carrier vesicles. These data implicate Tulp1 in the transport of selective integral membrane outer segment proteins and their associated proteins, specifically, the opsin and guanylate cyclase carrier pathways. The exact role of Tulp1 in outer segment protein transport remains elusive. However, without Tulp1, two rhodopsin transport machinery proteins exhibit abnormal distribution, Rab8 and Rab11, suggesting a role for Tulp1 in vesicular docking and fusion at the plasma membrane near the connecting cilium.
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