Tctex1d2 associates with short-rib polydactyly syndrome proteins and is required for ciliogenesis

Short-rib polydactyly syndromes (SRPS) arise from mutations in genes involved in retrograde intraflagellar transport (IFT) and basal body homeostasis, which are critical for cilia assembly and function. Recently, mutations in <i>WDR34</i> or <i>WDR60</i> (candidate dynein intermediate chains) were identified in SRPS. We have identified and characterized Tctex1d2, which associates with Wdr34, Wdr60 and other dynein complex 1 and 2 subunits. Tctex1d2 and Wdr60 localize to the base of the cilium and their depletion causes defects in ciliogenesis. We propose that Tctex1d2 is a novel dynein light chain important for trafficking to the cilium and potentially retrograde IFT and is a new molecular link to understanding SRPS pathology.

短肋多指综合征（Short-rib polydactyly syndromes, SRPS）的病因源于参与逆行鞭毛内运输（retrograde intraflagellar transport, IFT）以及基体稳态的基因发生突变，而上述过程对于纤毛的组装与功能发挥至关重要。近期，研究人员在SRPS患者中鉴定出WDR34或WDR60（候选动力蛋白中间链）的突变。本研究鉴定并表征了Tctex1d2，该蛋白可与Wdr34、Wdr60以及动力蛋白复合体1和2的其他亚基相结合。Tctex1d2与Wdr60均定位于纤毛基部，二者的表达缺失会导致纤毛发生缺陷。本研究提出，Tctex1d2是一种新型动力蛋白轻链，对于纤毛运输乃至潜在的逆行IFT过程具有重要作用，同时也是解析SRPS病理机制的全新分子关联靶点。