TrkB mutant lacking the amino-terminal half of the extracellular portion acts as a functional brain-derived neurotrophic factor receptor.

A series of mutants with deletion in the extracellular portion of TrkB were expressed transiently and stably in mammalian cells to examine the brain-derived neurotrophic factor (BDNF)-binding properties of TrkB. We found that these binding activities were retained by the TrkB deletion mutant (TrkBDelta4) lacking most of the extracellular portion, cysteine-rich cluster 1 and 2, leucine-rich motif and most of the first immunoglobulin-like domain (Ig1). Furthermore, the results of the neurotrophin selectivity, the equilibrium binding constant, auto-phosphorylation and BDNF dependent cell survival indicate that TrkBDelta4 acts as a functional BDNF receptor comparable to wild-type TrkB. Thus, our findings showed that only the carboxyl-terminal half of the extracellular portion of TrkB, which includes the Ig2 domain, is essential for the functional BDNF receptor.