Lasorella A et al. (2006) Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth. Nature 442: 471–474

Researchers in the US have elucidated part of the mechanism controlling the growth and differentiation of nerve cells, and their discovery might provide a means of promoting the regrowth of damaged neurons. The researchers investigated the role of Id2, a protein that promotes cell growth in the developing nervous system, but which is eliminated in mature neurons. Id2 is also abundantly expressed in many cancers. Id proteins inhibit transcription factors that promote cell differentiation, thereby locking cells into an unspecialized, dividing state.

The authors found that Id2 is destroyed by the anaphase-promoting complex (APC), an enzyme involved in cell-cycle regulation. The destruction of Id2 halts neuroblast cell division and leads to the development of mature neurons. The researchers produced a mutant Id2 protein that lacked the destruction sequence targeted by APC. Expression of this mutant protein led to prolonged axon growth in cerebellar granule neurons, cortical neurons and neuroblast cell lines; this effect could be reversed by the overexpression of E47, a transcription factor that drives differentiation of neurons and is normally inhibited by Id2. Mutant Id2 was able to stimulate axon growth even in the presence of myelin, which normally inhibits axon regrowth in damaged neurons.

Degradation-resistant Id2 offers the possibility of permitting damaged neurons to regenerate, with potential therapeutic applications for spinal cord damage and neurodegenerative conditions such as Alzheimer's disease.