DNM2

Cilia effects upon perturbation of DNM2

Cilia number / % ciliated:

Incrased cilia number

Loss-of-function effect:

Longer cilia

Ciliogenesis screen results (4 screens)

• Kim2016: Not Reported
• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-4.60) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Mouse phenotype:

decreased mean corpuscular volume, enlarged uterus, embryonic lethality prior to tooth bud stage, preweaning lethality, incomplete penetrance, decreased mean corpuscular hemoglobin, embryonic lethality prior to organogenesis, small superior vagus ganglion, increased circulating alkaline phosphatase level

Mouse ciliopathy phenotype:

hydrometra

Subcellular localization

basal body

Functional category

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

Function

Since PQBP1 inhibits Dynamin 2 activity, inhibition of Dynamin 2 would be predicted to induce the formation of the neuronal cilium. Consistent with this prediction, Dynamin 2 knockdown promoted ciliary morphogenesis in hippocampal neurons. The percentage of neurons harboring a primary cilium was increased, and the cilium was substantially longer in Dynamin 2 knockdown neurons, suggesting that Dynamin 2 inhibits the formation and growth of the primary cilium in neurons. In epistasis analyses, Dynamin 2 knockdown suppressed the PQBP1 knockdown-induced phenotype of loss of cilia, suggesting that Dynamin 2 operates downstream of PQBP1 in the control of ciliary morphogenesis.Dynamin 2-GFP fusion protein partially colocalized with the centrosomal marker Pericentrin and PQBP1 in neurons(PMID: 23994472).