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Phenotypes

Mouse phenotype:

short tibia

Subcellular localization

basal body, cilia, Centriolar satellite, Cytosol

Functional category

• Metabolism
• Motile cilium & axoneme
• Non-motile cilium / primary cilium
• Cilia–cytoskeleton/adhesion links

Function

To test whether MDM1 is a centrosome/cilia component we expressed a MDM1-GFP fusion protein in NIH/3T3 cells. MDM1-GFP localized to centrosomes, as determined by colocalization with gamma-tubulin (Figure 7A) and to the primary cilium, as determined by colocalization with acetylated alpha-tubulin (Figure 7B). Based on these results we suggest that the age-related retinal degeneration phenotype observed in the aard2 mouse results from a defect in connecting cilium function(23300604). We show that the MDM1 protein localizes to centrioles of dividing cells and differentiating multiciliated cells. 3D-SIM microscopy showed that MDM1 is closely associated with the centriole barrel, likely residing in the centriole lumen. Overexpression of MDM1 suppressed centriole duplication, whereas depletion of MDM1 resulted in an increase in granular material that likely represents early intermediates in centriole formation. We show that MDM1 binds microtubules in vivo and in vitro. We identified a repeat motif in MDM1 that is required for efficient microtubule binding and found that these repeats are also present in CCSAP, another microtubule-binding protein. We propose that MDM1 is a negative regulator of centriole duplication and that its function is mediated through microtubule binding(26337392). Upregulated during ciliogenesis (23300604). Microtubule- binding protein. Negative regulator of centriole duplication through microtubule binding. Overexpression of MDM1 suppresses centriole duplication and results in stabilization of (26337392). It might interact with members of the Hedgehog signaling pathway, as this pathway is tightly linked with cilia (27658201).