Volume 272, Number 20,
Issue of May 16, 1997
pp. 13019-13025
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
TrkB Variants with Deletions in the Leucine-rich Motifs of the
Extracellular Domain
(Received for publication, October 22, 1996, and in revised form, March 5, 1997)
Natalia
Ninkina
,
Marina
Grashchuck
,
Vladimir L.
Buchman
and
Alun M.
Davies
From the School of Biological and Medical Sciences, University of
St. Andrews, St. Andrews, Fife KY16 9AJ, Scotland
We have isolated two novel variants involving the
extracellular domain of TrkB from developing sensory neurons. These
variants are generated by alternative splicing and lack two or all
three of the leucine-rich motifs. Each of these variants is expressed as isoforms that possess or lack the intracellular tyrosine kinase domain. Fibroblast cell lines stably expressing these variants do not
bind any of the TrkB ligands (brain-derived neurotrophic factor,
neurotrophin-3, and neurotrophin-4/5) and neither survive nor undergo
morphological transformation in response to neurotrophins. These
results demonstrate that the leucine-rich motifs in TrkB are essential
for ligand binding and signaling and indicate that the extracellular
immunoglobulin-like domains alone are insufficient to confer
neurotrophin binding to TrkB.