Kif17 phosphorylation regulates photoreceptor outer segment turnover
Kif17 phosphorylation regulates photoreceptor outer segment turnover
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DOI：
10.1186/s12860-018-0177-9
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发表时间：
2018-11-20
期刊：
影响因子：
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通讯作者：
Besharse, Joseph C.
中科院分区：
文献类型：
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作者：
Lewis, Tylor R.;Kundinger, Sean R.;Besharse, Joseph C.
背景KIF 17是一种驱动蛋白-2马达，参与鞭毛内转运，可调控光感受器外节的发育。然而，KIF 17在成熟光感受器中的功能仍不清楚。此外，KIF 17的纤毛定位由C-末端共有序列（KRKK）调节，该序列紧邻先前显示被CaMKII磷酸化的保守残基（小鼠S1029/斑马鱼S815）。然而，这种磷酸化是否可以调节的本地化，从而在睫状体photoreceptors的功能，KIF 17仍然unknowed.ResultsUsing转基因表达在斑马鱼的光感受器，我们表明，磷酸模拟KIF 17增强本地化沿着锥外段。重要的是，磷酸化模拟KIF 17的表达与通过细胞自主方式的椎间盘脱落大大增强的光感受器外节的周转有关，而斑马鱼和小鼠中的kif 17基因突变体减少了椎间盘脱落。最后，组成型活性tCaMKII的锥表达导致一个KIF 17依赖性增加光盘shedding. ConclusionsTogether，我们的数据支持一个模型，其中KIF 17的磷酸化促进其光感受器外节本地化和光盘脱落，一个过程中必不可少的光感受器的维护和稳态。虽然光盘脱落主要是在视网膜色素上皮细胞吞噬外节的机制的背景下进行了研究，这项工作涉及光感受器衍生的信号在光盘脱落的基础机制。
BackgroundKIF17, a kinesin-2 motor that functions in intraflagellar transport, can regulate the onset of photoreceptor outer segment development. However, the function of KIF17 in a mature photoreceptor remains unclear. Additionally, the ciliary localization of KIF17 is regulated by a C-terminal consensus sequence (KRKK) that is immediately adjacent to a conserved residue (mouse S1029/zebrafish S815) previously shown to be phosphorylated by CaMKII. Yet, whether this phosphorylation can regulate the localization, and thus function, of KIF17 in ciliary photoreceptors remains unknown.ResultsUsing transgenic expression in zebrafish photoreceptors, we show that phospho-mimetic KIF17 has enhanced localization along the cone outer segment. Importantly, expression of phospho-mimetic KIF17 is associated with greatly enhanced turnover of the photoreceptor outer segment through disc shedding in a cell-autonomous manner, while genetic mutants of kif17 in zebrafish and mice have diminished disc shedding. Lastly, cone expression of constitutively active tCaMKII leads to a kif17-dependent increase in disc shedding.ConclusionsTaken together, our data support a model in which phosphorylation of KIF17 promotes its photoreceptor outer segment localization and disc shedding, a process essential for photoreceptor maintenance and homeostasis. While disc shedding has been predominantly studied in the context of the mechanisms underlying phagocytosis of outer segments by the retinal pigment epithelium, this work implicates photoreceptor-derived signaling in the underlying mechanisms of disc shedding.