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On the role of the low-affinity neurotrophin receptor p75LNTR in nerve growth factor induction of differentiation and AP 1 binding activity in PC12 cells

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Abstract

Three clones of PC12 cells that differ with respect to their nerve growth factor (NGF) receptors were examined: wild-type PC12 cells that have both trkA and p75LNTR receptors; the MR-1 clone that possesses a normal trkA receptor and a truncated form of p75LNTR without the extracellular NGF-binding part; and a new PC12 variant, called v-clone, that is partly characterized here. The v-clone had no demonstrable binding to trkA, but displayed binding to p75LNTR as assessed by chemical crosslinking. NGF did not induce any change in the tyrosine phosphorylation of phosphatidy-3′-kinase in the v-clone. NGF induced neurite extension in wild-type cells, induced it more rapidly in mR-1, but not at all in v-clone cells. The v-clone lacked the b-form of protein kinase C, but transfection with this enzyme did not restore responsiveness to NGF. Neurite extension in response to staurosporine and basic fibroblast growth factor was equal in wild-type and v-clone cells. All three clones responded to forskolin, with the mR-1 clone the most responsive.

NGF stimulated AP 1 binding activity in all clones. The response was transient in the MR-1 clone but prolonged in the wild-type and v-clone cells. In the wild-type and MR-1 clone cells, AP 1 binding activity was reduced by a tyrphostin analog, whereas in the v-clone cells it was inhibited by staurosporine. NGF increased inositol (1,4,5)-trisphosphate (InsP3) formation in all clones. In the wild-type and v-clone cells the InsP3 responses were followed by [Ca2+]i increases.

It is concluded that although trkA is required for differentiation in response to NGF in PC12 cells, the concomitant stimulation, by NGF, of p75LNTR may affect phospholipase C and AP 1. This may be important for the reported ability of p75LNTR to modify the phenotypic changes induced in PC12 cells by NGF.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Section of Molecular Neuropharmacology, Poland

    Ewa Kontny, Francisco Ciruela, Per Svenningsson & Bertil B. Fredholm

  2. Department of Pathophysiology and Immunology, Institute of Rheumatology, Warsaw, Poland

    Ewa Kontny

  3. Departmento de Bioquímica i Fisiologia, Facultat de Química, Universitat de Barcelona, Catalonia, Spain

    Francisco Ciruela

  4. Department of Medical Biochemistry and Biophysics, Laboratory of Molecular Neurobiology, Karolinska Institutet, Stockholm, Sweden

    Carlos F. Ibáñez

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  1. Ewa Kontny
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Kontny, E., Ciruela, F., Svenningsson, P. et al. On the role of the low-affinity neurotrophin receptor p75LNTR in nerve growth factor induction of differentiation and AP 1 binding activity in PC12 cells. J Mol Neurosci 8, 29–44 (1997). https://doi.org/10.1007/BF02736861

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