Translin-associated factor-X (Trax) is a molecular switch of growth-associated protein (GAP)-43 that controls axonal regeneration.

The ability of neurons to form axons requires the choreographed assembly of growth cones. We show that there is a time window from postnatal day 14 (P14) until P21/22 when axons of rat retinal ganglion cells will regenerate under serum-free culture conditions. In contrast, no outgrowth occurred before P13, and growth declined from P22 and ceased after P30. Using proteomics, we have identified translin-associated factor X (Trax), a DNA-binding factor that is expressed during this period of postnatal development. Trax is shown to coexpress with growth-associated protein GAP-43. Small interfering RNA-mediated inhibition of Trax expression resulted in downregulation of both Trax and GAP-43 transcripts and protein both before and during the period of regeneration (P8) and (P16). In contrast, silencing of Trax at P30 resulted in significant upregulation of the GAP-43 transcript and protein and induced outgrowth of axons. These data suggest that Trax regulates GAP-43 transcription and regeneration-promoting effects during the postnatal maturation period. Trax may represent a new potent therapeutic target gene for optic nerve and spinal cord injuries.