Tulp1 Is Involved in Specific Photoreceptor Protein Transport Pathways
Tulp1 Is Involved in Specific Photoreceptor Protein Transport Pathways
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DOI：
10.1007/978-1-4614-0631-0_100
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发表时间：
2012-01-01
期刊：
影响因子：
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通讯作者：
Grossman, Gregory H.
中科院分区：
文献类型：
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作者：
Hagstrom, Stephanie A.;Watson, Rao F.;Grossman, Gregory H.
Tulp1在蛋白从光感受器内段（IS）转运到外段（OS）的过程中起关键作用。为了分析在缺乏Tulp1的情况下，哪些OS蛋白的转运途径受到影响，我们调查了用于OS inulp1−/−小鼠的蛋白的定位。免疫组织化学用于检测视网膜变性前年轻tulp1−/−小鼠中几种OS蛋白以及参与OS蛋白运输的蛋白的定位。与野生型幼崽进行了比较。Tulp1的缺失不影响几种光导和OS结构蛋白的转运，包括磷酸二酯酶、视紫红质激酶、ROM-1、外周蛋白/RDS和阳离子通道。然而，其他光传导蛋白如视紫红质、视锥蛋白、鸟苷酸环化酶1和鸟苷酸环化酶激活蛋白1和2被错误定位到其他光感受器区室。两种响应光刺激易位的蛋白在1−/−视网膜中受到不同的影响；转导蛋白的易位是正确的，而抑制蛋白则没有。此外，在含有视紫红质的后高尔基囊泡运输中起关键作用的伴侣蛋白Rab6、Rab8和Rab11在p1−/−视网膜中受到严重破坏。我们得出结论，Tulp1是特定整体膜蛋白及其各自结合伙伴的正确运输所必需的。其他类别的OS驻留蛋白似乎不受影响。这些差异支持了Tulp1在光感受器OS蛋白转运途径中起特定关键作用的假设。
Tulp1 plays a critical role in protein transport from the photoreceptor inner segment (IS) to the outer segment (OS). To dissect which OS protein transport pathways are affected in the absence of Tulp1, we surveyed the localization of proteins destined for the OS intulp1−/−mice. Immunohistochemistry was used to examine the localization of several classes of OS proteins as well as proteins involved in OS protein transport in youngtulp1−/−mice prior to retinal degeneration. Comparisons were made to wild-type littermates. The absence of Tulp1 did not affect the transport of several phototransduction and OS structural proteins including phosphodiesterase, rhodopsin kinase, ROM-1, peripherin/RDS, and the cation channel. However, other phototransduction proteins such as rhodopsin, cone opsins, guanylate cyclase 1, and guanylate cyclase-activating proteins 1 and 2 were mislocalized to additional photoreceptor compartments. Two proteins that translocate in response to light stimulation were affected differently intulp1−/−retinas; transducin translocated correctly whereas arrestin did not. In addition, chaperone proteins critical in the transport of rhodopsin-containing post-Golgi vesicles, Rab6, Rab8, and Rab11, were severely disrupted intulp1−/−retinas. We conclude that Tulp1 is required for the correct transport of specific integral membrane proteins and their respective binding partners. Other classes of OS resident proteins do not appear to be affected. These differences support the hypothesis that Tulp1 plays a specific, critical role in photoreceptor OS protein transport pathways.