Developmental co-expression and functional redundancy of tyrosine phosphatases with neurotrophin receptors in developing sensory neurons.
Receptor-type protein tyrosine phosphatases (RPTPs) have been implicated as direct or indirect regulators of neurotrophin receptors (TRKs). It remains less clear if and how such RPTPs might regulate TRK proteins in vivo during development. Here we present a comparative expression profile of RPTP genes and Trk genes during early stages of murine, dorsal root ganglion maturation. We find little if any specific, temporal mRNA co-regulation between individual RPTP and Ntrk genes between E12.5 and E14.5. Moreover, a double fluorescent in-situ hybridization and immunofluorescence study of seven Rptp genes with Ntrks revealed widespread co-expression of RPTPs in individual neurons, but no tight correlation with Trk expression profiles. No Rptp is expressed in 100% of Ntrk1-expressing neurons, whereas at least 6 RPTPs are expressed in 100% of Ntrk2- and Ntrk3-expressing neurons. An exception is Ptpro, which showed very selective expression. Short hairpin RNA suppression of Ptprf, Ptprs or Ptpro in primary, E13.5 DRG neurons did not alter TRK signalling. We therefore propose that TRK signalling may not be simply dependent on rate-limiting regulation by individual RPTP subtypes during sensory neuron development. Instead, TRK signalling has the potential to be buffered by concurrent inputs from several RPTPs in individual neurons.
Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, United Kingdom.
Viktoria
V
Tchetchelnitski
MERCK SERONO SA.-Geneva, 9 Chemin des Mines, CH-1202 Geneve, Switzerland.
Monique
M
van den Eijnden
MERCK SERONO SA.-Geneva, 9 Chemin des Mines, CH-1202 Geneve, Switzerland.
Fanny
F
Schmidt
Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, United Kingdom. Electronic address: a.stoker@ucl.ac.uk.
Andrew W
AW
Stoker
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000166:cytology* / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D000076223:Regulatory-Associated Protein of mTOR; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017475:Receptors, Nerve Growth Factor; D000076223:Regulatory-Associated Protein of mTOR; C540162:Rptor protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D017027:Protein Tyrosine Phosphatases
DRG; Neurotrophin; PTP; Protein tyrosine phosphatase; Sensory neuron; TRK signalling