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.
Schröer
Uwe
U
Department of Experimental Ophthalmology, School of Medicine, University Eye Hospital Münster, Domagkstrasse 15, 48149 Münster, Germany.
Volk
Gerd Fabian
GF
Liedtke
Tomas
T
Thanos
Solon
S
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004268:DNA-Binding Proteins / Q000502:physiology*; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D019922:GAP-43 Protein / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology*; D012165:Retinal Ganglion Cells / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D004268:DNA-Binding Proteins; D019922:GAP-43 Protein; D007211:Indoles; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C498307:Tsnax protein, rat; C007293:DAPI