DBN1

Cilia effects upon perturbation of DBN1

Loss-of-function effect:

Shorter cilia

Overexpression effect:

longer cilia

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-2.06) 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 total body fat amount, increased bone mineral content, decreased vertical activity, increased circulating phosphate level, decreased total reti thickness, abnormal coat appearance, increased circulating alkaline phosphatase level, increased circulating chloride level, decreased body weight, increased prepulse inhibition, increased exploration in new environment, preweaning lethality, complete penetrance, abnormal allantois morphology, preweaning lethality, incomplete penetrance, increased circulating magnesium level, increased red blood cell distribution width, increased cd8-positive, alpha-beta t cell number, decreased circulating serum albumin level, hyperactivity, abnormal embryo size, decreased circulating fructosamine level, decreased mean platelet volume, decreased circulating hdl cholesterol level, no spontaneous movement, increased fasting circulating glucose level, abnormal chorioallantoic fusion, unresponsive to tactile stimuli, increased lean body mass, increased leukocyte cell number, decreased grip strength, increased bone mineral density, abnormal vertebrae morphology, decreased circulating free fatty acids level, decreased circulating cholesterol level

Mouse ciliopathy phenotype:

abnormal embryo turning, abnormal liver morphology, enlarged heart, increased circulating creatinine level, abnormal heart morphology, increased heart weight

Subcellular localization

cilia

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Actin & cytoskeleton regulation
• T cell biology
• Neurogenesis & migration
• Signaling (Hedgehog, GPCRs, ion channels)
• Cilia length regulation

Function

DBN1 and hCDC14A contribute to cilia length control by regulating the actin nucleator Arp2 at the basal body. hCDC14A has additio l, DBN1 independent functions in endocytosis and transport of myosin Va marked vesicles to the basal body(30467237). Overexpression of DBN1 or RPE1 WT cells significantly increased cilia length.