TBC1D20

Cilia effects upon perturbation of TBC1D20

Cilia number / % ciliated:

Incrased cilia number

Loss-of-function effect:

No effect

Ciliogenesis screen results (5 screens)

• Kim2016: No effect
• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-2.22) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381
• Kim et al. 2010 (siRNA) [siRNA]: Longer Cilia (Area per Cilia z=3.70) PMID:20393562

Phenotypes

Mouse phenotype:

abnormal skin morphology, no spontaneous movement, hemorrhage, increased red blood cell distribution width

Mouse ciliopathy phenotype:

male infertility, increased heart weight

Subcellular localization

cilia associated gene

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• Reproduction & sperm
• Viral interactions

Function

Depletion of TBC1D20 promotes Rab11 vesicle accumulation and actin deconstruction around the centrosome, facilitating the initiation of ciliogenesis even in cycling cells. Further investigations reveal enhanced Rab11–MICAL1 interaction upon TBC1D20 loss, activating the monooxygenase domain of MICAL1 and inducing F-actin depolymerization around the centrosome. This actin network reorganization facilitates vesicle trafficking and docking, ultimately promoting ciliogenesis. In summary, our work uncovers a coordinated ciliogenesis initiation mechanism via Rab11 activation. These findings underscore a pivotal role for TBC1D20 in early ciliogenesis, advancing our understanding of its spatiotemporal regulation and offering insights into the disease pathogenesis associated with TBC1D20 mutations. TBC1D20 depletion significantly increased the percentage of ciliated cells after 24 h of serum starvation without altering the average cilium length. (39868814)