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Expression of the naturally occurring truncated trkB neurotrophin receptor induces outgrowth of filopodia and processes in neuroblastoma cells

Oncogene volume 18, pages 1285–1296 (1999)Cite this article

Abstract

We have investigated the effects of the truncated trkB receptor isoform T1 (trkB.T1) by transient transfection into mouse N2a neuroblastoma cells. We observed that expression of trkB.T1 leads to a striking change in cell morphology characterized by outgrowth of filopodia and processes. A similar morphological response was also observed in SH-SY5Y human neuroblastoma cells and NIH3T3 fibroblasts transfected with trkB.T1. N2a cells lack endogenous expression of trkB isoforms, but express barely detectable amounts of its ligands, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4). The morphological change was ligand-independent, since addition of exogenous BDNF or NT-4 or blockade of endogenous trkB ligands did not influence this response. Filopodia and process outgrowth was significantly suppressed when full-length trkB.TK+ was cotransfected together with trkB.T1 and this inhibitory effect was blocked by tyrosine kinase inhibitor K252a. Transfection of trkB.T1 deletion mutants showed that the morphological response is dependent on the extracellular, but not the intracellular domain of the receptor. Our results suggest a novel ligand-independent role for truncated trkB in the regulation of cellular morphology.

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Acknowledgements

The authors would like to thank Ms Laila Kukkonen for excellent technical assistance and M.Sc. Nina Honka for the help in cloning the trkB cDNAs. We are grateful to Dr Alexander Parsadanian for generously providing the sequence for mouse NT-4, to Dr Louis Reichardt for the gift of REX antibody, to Dr Shigekazu Nagata for kindly providing the pEF-BOS expression vector, to Chris Burnett (Palo Alto Institute of Molecular Medicine) for the gift of red shift GFP, to Dr Teemu Teeri for providing the red shift GFP construct in pEF-BOS expression plasmid, and to Regeneron Pharmaceuticals for the gift of trkB-IgG. We would also like to thank Drs Heikki Rauvala, Antero Salminen and Ari Huovila for helpful discussions during this study. This study has been supported by the Academy of Finland EU Biotechnology grant (PL 970259), and Sigrid Juselius Foundation. AH and TS are Ph.D. students of the Finnish Graduate School for Neuroscience and A.I. Virtanen Institute Graduate School, respectively.

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  1. Tiila-Riikka Kiema

    Present address: Department of Biochemistry, University of Oulu, Finland

Authors and Affiliations

  1. Laboratory of Molecular Pharmacology, A.I. Virtanen Institute,, 70100, Kuopio, Finland

    Annakaisa Haapasalo, Tommi Saarelainen, Tiila-Riikka Kiema, Garry Wong & Eero Castrén

  2. Department of Psychiatry, University of Kuopio, 70100 Kuopio, PO Box 1627, Finland

    Eero Castrén

  3. Institute for Biotechnology, University of Helsinki, PO Box 56, Helsinki, 00014, Finland

    Maxim Moshnyakov, Urmas Arumäe & Mart Saarma

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Haapasalo, A., Saarelainen, T., Moshnyakov, M. et al. Expression of the naturally occurring truncated trkB neurotrophin receptor induces outgrowth of filopodia and processes in neuroblastoma cells. Oncogene 18, 1285–1296 (1999). https://doi.org/10.1038/sj.onc.1202401

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