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 WDR34 or WDR60 (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）由参与逆行鞭毛内运输（retrograde intraflagellar transport, IFT）与基体稳态（basal body homeostasis）的基因突变引发，而这两类过程对纤毛的组装与功能（cilia assembly and function）至关重要。近期研究发现，短肋多指综合征患者存在WDR34或WDR60（候选动力蛋白中间链（dynein intermediate chains））的突变。本研究已鉴定并表征了Tctex1d2，该蛋白可与Wdr34、Wdr60以及其他动力蛋白复合体1和2（dynein complex 1 and 2）的亚基结合。Tctex1d2与Wdr60定位于纤毛基部（base of the cilium），二者的敲低会导致纤毛发生（ciliogenesis）缺陷。本研究提出，Tctex1d2是一种新型动力蛋白轻链（dynein light chain），对纤毛运输乃至潜在的逆行鞭毛内运输均具有重要作用，同时也是阐释短肋多指综合征病理机制（pathology）的全新分子关联靶点。