We newly found that ZNRF1 induces cell morphological changes and that a RING finger domain is required for this neurite-like elongation. Unfortunately, we could not show ubiquitination of Tubb2 or acceleration of the turnover of Tubb2 by ZNRF1 (data not shown). However, since a RING finger domain of ZNRF1 is important for E3 ubiquitin ligase activity and for morphological changes, we cannot rule out the possibility that proteins other than Tubb2 are substrates for ZNRF1. It has also been reported that a large multidomain E3 ubiquitin ligase Phr1 is associated with the microtubule
A-769662 within neurons and selectively is localized to
axons but is excluded from growth cones and that motor and sensory neurons from Magellan mice in which the Phr1 gene is mutated displays abnormal morphologies. It has been reported that the E3 ubiquitin ligase Parkin, the gene of which has several mutations in autosomal-recessive juvenile Parkinsonism (ARJP), binds to tubulin heterodimers and accelerates degradation of α- and β-tubulin [14], resulting in possible protection by Parkin of neurons from the toxic accumulation of misfolded tubulin. Taken together, tubulin modification by ubiquitination may be important for neuritogenesis and intracellular quality-control for neurons.
