The receptor tyrosine kinase TrkB signals without dimerization at the plasma membrane

Eitan Erez Zahavi, Noam Steinberg, Topaz Altman, Michael Chein, Yuvraj Joshi, Tal Gradus-Pery, Eran Perlson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Tropomyosin-related tyrosine kinase B (TrkB) is the receptor for brain-derived neurotrophic factor (BDNF) and provides critical signaling that supports the development and function of the mammalian nervous system. Like other receptor tyrosine kinases (RTKs), TrkB is thought to signal as a dimer. Using cell imaging and biochemical assays, we found that TrkB acted as a monomeric receptor at the plasma membrane regardless of its binding to BDNF and initial activation. Dimerization occurred only after the internalization and accumulation of TrkB monomers within BDNF-containing endosomes. We further showed that dynamin-mediated endocytosis of TrkB-BDNF was required for the effective activation of the kinase AKT but not of the kinase ERK1/2. Thus, we report a previously uncharacterized mode of monomeric signaling for an RTK and a specific role for the endosome in TrkB homodimerization.

Original languageEnglish
Article number4006
JournalScience Signaling
Volume11
Issue number529
DOIs
StatePublished - 8 May 2018

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