PDCD6IP

Cilia effects upon perturbation of PDCD6IP

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-4.05) 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:

abnormal lymph node morphology, enlarged spleen, decreased brain size, increased circulating hdl cholesterol level, abnormal spleen morphology, abnormal behavior, increased grip strength, decreased anxiety-related response, abnormal stomach morphology, increased red blood cell distribution width, decreased circulating bilirubin level, increased exploration in new environment, hypoplasia, decreased body length, decreased locomotor activity, decreased heart weight, abnormal lung morphology, decreased food intake, abnormal eye morphology, enlarged lymph nodes, thick skin, abnormal semil vesicle morphology, atrophy, abnormal skin morphology, increased blood urea nitrogen level, decreased thigmotaxis, decreased brain weight, enlarged stomach, decreased heart rate

Mouse ciliopathy phenotype:

abnormal testis morphology, abnormal brain morphology, small kidney, abnormal kidney morphology, small testis, hydrocephaly, microphthalmia, hydrocephalus, polycystic kidney

Subcellular localization

basal body, cytosol, endosome

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation
• Viral interactions
• Signaling (Hedgehog, GPCRs, ion channels)

Function

In a knockout mouse model of Alix, defined overt structural changes in the epithelium of the choroid plexus and in the ependyma, such as asymmetrical cell shape and size, misplacement and abnormal beating of cilia, blebbing of the microvilli (27336173).PDCD6IP localized to basal body (25613900). ALIX, a protein previously linked to the biogenesis of small extracellular vesicles, as a novel component localized at the base of primary cilia in cultured mammalian cells. We show that ALIX retention at this site requires the ciliary kinesin-3 motor protein KIF13B, which physically interacts with ALIX and the E3 ubiquitin ligase ITCH. In turn, ITCH is enriched at the ciliary base and is essential for ALIX stability. Depletion of either ALIX or ITCH results in elevated ciliary levels of Polycystin-2, while ITCH loss additionally leads to constitutive accumulation of Smoothened, a key Sonic hedgehog effector, within the cilium. Collectively, our findings establish ALIX and ITCH as critical regulators of ciliary membrane protein homeostasis and signaling, acting in coordination with KIF13B to maintain proper ciliary function(PMID: 41742018).