DYNC2I2

Cilia effects upon perturbation of DYNC2I2

Phenotypes

Human ciliopathy phenotype:

Short rib-polydactyly syndrome, Verma-Naumoff type

Ciliopathy associations

• Cone-Rod Dystrophy
• Short-Rib Thoracic Dysplasia

Subcellular localization

basal body, cilia

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• Signaling (Hedgehog, GPCRs, ion channels)
• Transition zone

Function

Dynein intermediate chain associated with the retrograde intraflagellar transport motor dynein 2 (25205765). Orthologous to Chlamydomo s FAP133 and Trypanosome DIC5 (24989795). Homozygous missense mutations cause short-rib polydactyly syndrome type III/severe asphyxiating thoracic dysplasia (OMIM:, 24183449, 24183451). Acts as a TAK1-associated suppressor of the IL- 1R/TLR3/TLR4-induced NF- 魏B activation pathway. Patient fibroblast cilia are short with a bulbous tip (24183449). Localises around basal bodies, centrioles and along the axoneme (24183451). Interacts with DYNLL1 and DYNLL2 (25294941), TCTEX1D2 (25830415). Required for retrograde IFT and Hedgehog sig lling in mouse (28379358). WDR34 KO cells can assemble a dynein-2 motor complex that binds IFT proteins yet fails to extend an axoneme (30320547). Incorporation of DYNLL1/DYNLL2 and DYNLRB1/DYNLRB2 into the dynein-2 complex via interactions with the WDR34 intermediate chain is crucial for dynein-2 function in retrograde ciliary protein trafficking (30649997), Dynein 2 intermediate chain. Biallelic truncating, frameshift or missense mutations cause autosomal recessive short-rib thoracic dysplasia type 8 with or without polydactyly (OMIM:615462) (23910462). Localizes to the base of the cilium in human chondrocytes (23910462), RPE1 cells (25205765) and HEK293 cells (25830415). Ciliogenesis is inhibited in fibroblasts from affected patients, GLI2 accumulates at basal body (23910462). Stability of WDR34 and WDR60 is interdependent (25205765). Localises to the centrosome in interphase, the spindle poles during mitosis and cytokinesis, and near the cytokinetic bridge during cytokinesis in HeLa cells (25830415). Interaction with TCTEX1D2 light chain of the dynein-2 complex is crucial for ciliary protein trafficking. (29742051).WDR60 KO cells extend axonemes but show reduced assembly of dynein-2 and binding to IFT proteins. Required to maintain a functio l transition zone and for efficient bidirectio l intraflagellar transport (30320547, 30649997). Structure resolved in 31451806