Truncated Trk Action

Neurotrophins promote neuron survival and maturation and support the development and function of neural tissue and organs. They bind to and activate receptor tyrosine kinases of the Trk family. However, truncated forms of TrkB and TrkC that lack the intracellular kinase domain are expressed primarily in glial cells, and their function has not been so clear. They have been presumed to play a passive role, sequestering neurotrophins or inhibiting full-length receptors through dimerization. Rose et al. combined calcium imaging and electrophysiology to observe a direct role of a truncated form TrkB (TrkB-T1) in mediating the effects of brain-derived neurotrophic factor (BDNF) in cultured astrocytes and glia. BDNF evoked a transient increase in intracellular calcium that required the activation of phospholipase C (PLC), which generates inositol trisphosphate (IP 3 ), and a heterotrimeric GTP-binding protein (G protein) that is insensitive to pertussis toxin. The calcium wave was blocked by an inhibitor of the IP 3 receptor that controls calcium release from intracellular compartments. The expression of TrkB-T1 was more than 100 times that of full-length TrkB in glia, and BDNF-induced currents were the same in glia derived from either wild-type mice or mice lacking full-length TrkB. Reduction of TrkB1-T1 expression by an antisense approach reduced the amplitude of BDNF-evoked calcium transients by 45%. The authors propose that TrkB1-T1 stimulates the release of calcium from intracellular stores through a G protein-PLC-IP 3 receptor pathway in astroctyes and glia. This may control the release of neurotransmitters and other molecules that affect neuron function. C. R. Rose, R. Blum, B. Pichler, A. Lepier, K. W. Kafits, A. Konnerth, Truncated TrkB1-T1 mediates neurotrophin-evoked calcium signalling in glia cells. Nature 426 , 74-78 (2003). [Online Journal]