Figure 5. Schematic model illustrating proposed roles for wild-type (A) and ALS-associated UBQLN4D90A (B) in motor axon morphogenesis.
(A) Wild-type UBQLN4 associates with beta-catenin through its UBA domain, and with the proteasome through its UBL domain. These interactions allow for the degradation of beta-catenin, which in turn modulates gene expression to control motor axon morphogenesis. (B) The ALS-associated UBQLN4D90A variant is deficient in mediating proteasomal degradation of beta-catenin, leading to its accumulation and excessive induction of gene expression. Hyperactivation of beta-catenin-controlled genes dysregulates axon morphogenesis, causing aberrant axon branching in motor neurons.