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该构造复合物调节光感受器纤毛中的膜蛋白组成。

The tectonic complex regulates membrane protein composition in the photoreceptor cilium.

机构信息

Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI, USA.

Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, USA.

出版信息

Nat Commun. 2023 Sep 13;14(1):5671. doi: 10.1038/s41467-023-41450-z.

Abstract

The primary cilium is a signaling organelle with a unique membrane composition maintained by a diffusional barrier residing at the transition zone. Many transition zone proteins, such as the tectonic complex, are linked to preserving ciliary composition but the mechanism remains unknown. To understand tectonic's role, we generate a photoreceptor-specific Tctn1 knockout mouse. Loss of Tctn1 results in the absence of the entire tectonic complex and associated MKS proteins yet has minimal effects on the transition zone structure of rod photoreceptors. We find that the protein composition of the photoreceptor cilium is disrupted as non-resident membrane proteins accumulate in the cilium over time, ultimately resulting in photoreceptor degeneration. We further show that fluorescent rhodopsin moves faster through the transition zone in photoreceptors lacking tectonic, which suggests that the tectonic complex acts as a physical barrier to slow down membrane protein diffusion in the photoreceptor transition zone to ensure proper removal of non-resident membrane proteins.

摘要

初级纤毛是一种信号细胞器,具有独特的膜组成,由位于过渡区的扩散屏障维持。许多过渡区蛋白,如 tectonic 复合物,与维持纤毛组成有关,但机制尚不清楚。为了了解 tectonic 的作用,我们生成了一种光感受器特异性的 Tctn1 敲除小鼠。Tctn1 的缺失导致整个 tectonic 复合物和相关的 MKS 蛋白缺失,但对杆状光感受器过渡区的结构几乎没有影响。我们发现,随着时间的推移,非驻留膜蛋白在纤毛中积累,光感受器纤毛的蛋白组成被破坏,最终导致光感受器变性。我们进一步表明,在缺乏 tectonic 的光感受器中,荧光视蛋白通过过渡区的速度更快,这表明 tectonic 复合物作为一种物理屏障,减缓了光感受器过渡区中膜蛋白的扩散,以确保适当去除非驻留膜蛋白。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08a8/10500017/bf3f841f41a1/41467_2023_41450_Fig1_HTML.jpg

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