Abstract
Glial cell line-derived neurotrophic factor (GDNF), an important factor for develo** and lesioned pre- and postganglionic sympathetic neurons, and its congeners signal through a receptor complex consisting of the tyrosine kinase c-Ret and a lipid-anchored α receptor (GFRα-1-4). Using in situ hybridization we show now that the mRNA for GFRα-2 is abundant in the adult rat adrenal medulla and its chromaffin cells. Coexpression of c-Ret and GFRα-1 mRNA's is restricted to a scarce subpopulation of medullary sympathetic neurons. Both GFRα-1 and GFRα-2 mRNA's are associated with preganglionic nerve trunks in the adrenal cortex. It is conceivable therefore that GDNF and related factors may activate chromaffin and preganglionic Schwann cells through a GFR-α receptor in absence of c-Ret.
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AIRAKSINEN, M. S., TITIEVSKY, A. & SAARMA, M. (1999) GDNF family neurotrophic factor signaling: Four masters, one servant? Molecular and Cellular Neuroscience 13, 313-325.
BALOH, R. H., TANSEY, M. G., GOLDEN, J. P., CREEDON, D. J., HEUCKEROTH, R. O., KECK, C. L., ZIMONJIC, D. B., POPESCU, N. C., JOHNSON, E. M. JR. & MILBRANDT, J. (1997) TrnR2, a novel receptor that mediates neurturin and GDNF signaling through Ret. Neuron 18, 793-802.
BUJ-BELLO, A., ADU, J., PINON L. G., HORTON, A., THOMPSON, J., ROSENTHAL, A., CHINCHETRU, M., BUCHMAN, V. L. & DAVIES, A. M. Neurturin responsiveness requires a GPI-linked receptor and the Ret receptor tyrosine kinase. Nature 387, 721-724.
BUJ-BELLO, A., BUCHMAN, V. L., HORTON, A., ROSENTHAL, A. & DAVIES, A. M. (1995) GDNF is an age specific survival factor for sensory and autonomic neurons. Neuron 15, 821-828.
HENDERSON, C. E., PHILLIPS, H. S., POLLOCK, R. A., DAVIES, A. M., LEMEULLE, C., ARMANINI, M., SIMMONS, L., MOFFET, B., VANDLEN, R. A., KOLIATSOS, V. E. & ROSENTHAL, A. (1994) GDNF: A potent survival factor for motoneurons present in peripheral nerve and muscle. Science 266, 1062-1064.
HEUCKEROTH, R. O., ENOMOTO, H., GRIDER, J. R., GOLDEN, J. P., HANKE, J. A., JACKMAN, A., MOLLIVER, D. C., BARDGETT, M. E., SNIDER, W. D., JOHNSON, E. M. JR. & MILBRANDT, J. (1999) Gene targeting reveals a critical role for neurturin in the development and maintenance of enteric, sensory, and parasympathetic neurons. Neuron 22, 253-263.
HOLGERT, H., DAGERLIND, A. & HÖKFELT, T. (1996) Phenotype of intraadrenal ganglion neurons during postnatal development in rat. Journal of Comparative Neurology 371, 603-620.
JASZAI, J., FARKAS, L., GALTER, D., REUSS, B., STRELAU, J., UNSICKER, K. & KRIEGLSTEIN, K. (1998) GDNF-related factor persephin is widely distributed throughout the nervous system. Journal of Neuroscience Research 53, 494-501.
JING, S., WEN, D., YU, Y., HOLST, P. L., LUO, Y., FANG, M., TAMIR, R., ANTONIO, L., HU, Z., CUPPLES, R., LOUIS, J. C., HU, S., ALTROCK, B. W., FOX, G. M. (1996). GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF. Cell 28, 1113-1124.
KRIEGLSTEIN, K., DEIMLING, F., SUTER-CRAZZOLARA, C. & UNSICKER, K. (1996) Expression and localization of GDNF in develo** and adult adrenal chromaffin cells. Cell and Tissue Research 286, 263-268.
KRIEGLSTEIN, K., HENHEIK, P., FARKAS, L., JASZAI, J., GALTER, D., KROHN, K. & UNSICKER, K. (1998) Glial cell line-derived neurotrophic factor requires transforming growth factor-beta for exerting its full neurotrophic potential on peripheral and CNS neurons. Journal of Neuroscience 18, 9822-9834.
LIN, L. F., DOHERTY, D. H., LILE, J. D., BEKTESH, S. & COLLINS, F. (1993) GDNF: A glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260, 1130-1132.
LUUKKO, K., SUVANTO P., SAARMA, M. & THESLEFF, I. (1997) Expression of GDNF and its receptors in develo** tooth is developmentally regulated and suggests multiple roles in innervation and organogenesis. Developmental Dynamics 210, 463-471.
POTERYAEV, D., TITIEVSKY, A., SUN, Y. F., THOMAS-CRUSELLS, J., LINDAHL, M., BILLAUD, M., ARUMÄE, U. & SAARMA, M. (1999) GDNF triggers a novel ret-independent Src kinase family-coupled signaling via a GPI-linked GDNF receptor alpha1. FEBS Letters 463, 63-66.
REEBEN, M., LAURIKAINEN, A., HILTUNEN, J. O., CASTREN, E & SAARMA, M. (1998) The messenger RNAs for both glial cell line-derived neurotrophic factor receptors, c-ret and GDNFR alpha, are induced in the rat brain in response to kainate-induced excitation. Neuroscience 83, 151-159.
SAARMA, M., & ARUMÄE, U. (1999) GDNF family: New promising neurotrophic factors. Neuroscience News 2, 26-34.
SANICOLA, M., HESSION, C., WORLEY, D., CARMILLO, P., EHRENFELS, C., WALUS, L., ROBINSON, S., JAWORSKI, G., WIE, H., TIZZARD, R., WHITTY, A., PEPINSKI, R. B. & CATE, R. L. (1997) Glial cell line-derived neurotrophic factor-dependent RET activation can be mediated by two different cell-surface accessory proteins. Proceedings of the National Acadamy of Sciences (USA) 94, 6238-6243.
SCHOBER, A., HERTEL, R., ARUMÄE, U., FARKAS, L., JASZAI, J., KRIEGLSTEIN, K., SAARMA, M. & UNSICKER, K. (1999) Glial cell line-derived neurotrophic factor rescues target-deprived sympathetic spinal cord neurons but requires transforming growth factor-beta as cofactor in vivo. Journal of Neuroscience 19, 2008-2015.
SEIDL, K., MANTHORPE, M., VARON, S. & UNSICKER, K. (1987) Differential effects of nerve growth factor and ciliary neuronotrophic factor on catecholamine storage and catecholamine synthesizing enzymes of cultured rat chromaffin cells. Journal of Neurochemistry 49, 169-174.
SUVANTO P., WARTIOVAARA K., LINDAHL M., ARUMÄE U., MOSHNYAKOV M., HORELLIKUITUNEN N., AIRAKSINEN, M. S., PALOTIE, A., SARIOLA, H. & SAARMA, M. (1997) Cloning, mRNA distribution and chromosomal localization of the gene for glial cell line-derived neurotrophic factor receptor beta, a homologue to GDNFR-alpha. Human Molecular Genetics 6, 1267-1273.
TRUPP, M., BELLUARDO, N., FUNAKOSHI, H. & IBANEZ, C. F. (1997) Complementary and overlap** expression of glial cell line-derived neurotrophic factor (GDNF), c-ret proto-oncogene, and GDNF receptoralpha indicates multiple mechanisms of trophic actions in the adult rat CNS. Journal of Neuroscience 17, 3554-3567.
TRUPP, M., RYDEN, M., JORNVALL, H., FUNAKOSHI, H., TIMMUSK, T., ARENAS, E. & IBANEZ, C. F. (1995) Peripheral expression and biological activities of GDNF, a new neurotrophic factor for avian and mammalian peripheral neurons. Journal of Cell Biology 130, 137-148.
UNSICKER, K., SUTER-CRAZZOLARA, C. & KRIEGLSTEIN, K. (1999) Neurotrophic roles of GDNF and related receptors. In Handbook of Experimental Pharmacology, Vol 137: Neurotrophic Factors, pp. 189-224. Berlin: Springer.
UNSICKER, K. & WESTERMANN, R. (1992) Basic fibroblast growth factor promotes transmitter storage and synthesis in cultured chromaffin cells. Developmental Brain Research 65, 211-216.
WEINER, N. (1975) Control of biosynthesis of adrenal catecholamines by the adrenal medulla. In Handbook of Physiology, Section 7: Endocrinology, Vol VI: Adrenal Gland, pp. 357-366. Washington D.C.: American Physiological Society.
YLIKOSKI, J., PIRVOLA, U., VIRKKALA, J., SUVANTO, P., LIANG, X. Q., MAGAL, E., ALTSCHULER, R., MILLER, J. M. & SAARMA, M. (1998) Guinea pig auditory neurons are protected by glial cell line-derived growth factor from degeneration after noise trauma. Hearing Research 124, 17-26.
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Schober, A., Arumäe, U., Saarma, M. et al. Expression of GFRα-1, GFRα-2, and c-Ret mRNAs in rat adrenal gland. J Neurocytol 29, 209–213 (2000). https://doi.org/10.1023/A:1026559225394
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DOI: https://doi.org/10.1023/A:1026559225394