ATXN3

Cilia effects upon perturbation of ATXN3

Loss-of-function effect:

Longer cilia

Overexpression effect:

Shorter cilia

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Pusapati et al. 2018 (CRISPR) [CRISPR]: Negative Regulator (Hh signaling, pos_rank=364, lfc=0.57) PMID:30270045

Phenotypes

Mouse phenotype:

increased anti-nuclear antigen antibody level, decreased circulating fructosamine level

Mouse ciliopathy phenotype:

increased circulating aspartate transamise level

Human ciliopathy phenotype:

Spinocerebellar ataxia type 3

Ciliopathy associations

• Spinocerebellar Ataxia

Subcellular localization

basal body, cilia, cytosol, nucleus

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation
• Transcription regulation

Function

ATXN3 localizes at the basal body and axoneme of the cilium, supporting its role in regulating ciliary length. Abrogation of Atxn3 expression causes decreased levels of the regulatory protein KEAP1 in the retina and delayed phagosome maturation in the retinal pigment epithelium. ATXN3 regulates two relevant biological processes in the retina, namely, ciliogenesis and phagocytosis, by modulating microtubule polymerization and microtubule-dependent retrograde transport, thus positing ATXN3 as a causative or modifier gene in retinal/macular dystrophies. On average, ATXN3-depleted cells showed statistically significantly longer cilia (with a 20% mean increase) than control-transfected cells (4.222 μm and 3.523 μm, respectively) (Figure 3E). On the contrary,on average, cilium length was 4.318 μm for control, 3.211 μm for ATXN3 WT, and 4.208 μm in cells overexpressing ATXN3 C14A (Figure 3G). (33176149).