Tropomyosin-Related Kinase B (TrkB) Regulates Neurite Outgrowth via a Novel Interaction with Suppressor of Cytokine Signalling 2 (SOCS2)

Akram Zamani, Junhua Xiao, Ann M. Turnley, Simon S. Murray

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Brain-derived neurotrophic factor (BDNF) is highly expressed in the hippocampus, where it can initiate signalling pathways leading to neurite outgrowth, neuron survival, spine maturation and increased synapse strength. Although suppressor of cytokine signalling 2 (SOCS2) is primarily known to negatively regulate cytokine signalling, it is also highly expressed in the hippocampus and exerts neuron-specific functions in the brain, effecting the length and architecture of neurons. However, little is known about the role of SOCS2 in the hippocampus. In this study, we hypothesised that SOCS2 may have a regulatory role in BDNF-dependent neurite growth and hippocampal neuronal function. Here our data demonstrate that SOCS2 interacts with the kinase domain of the BDNF receptor TrkB. Germline overexpression of SOCS2 results in a BDNF-dependent increase in hippocampal neurite outgrowth, whereas deletion of SOCS2 results in shorter neurite outgrowth. Expression of SOCS2 also results in increased ubiquitination of the juxtamembrane region of TrkB, and alters the trafficking of TrkB into recycling endosomes. Collectively, our data suggest a novel role for SOCS2 in interacting with and regulating the trafficking of TrkB, leading to increased neurite outgrowth in hippocampus neurons.

Original languageEnglish
Pages (from-to)1262-1275
Number of pages14
JournalMolecular Neurobiology
Volume56
Issue number2
DOIs
Publication statusPublished - 1 Feb 2019
Externally publishedYes

Keywords

  • BDNF
  • Endosome trafficking
  • SOCS2
  • TrkB
  • Ubiquitination

Cite this

@article{274e1b0794164f56aefc35c4a753b4fc,
title = "Tropomyosin-Related Kinase B (TrkB) Regulates Neurite Outgrowth via a Novel Interaction with Suppressor of Cytokine Signalling 2 (SOCS2)",
abstract = "Brain-derived neurotrophic factor (BDNF) is highly expressed in the hippocampus, where it can initiate signalling pathways leading to neurite outgrowth, neuron survival, spine maturation and increased synapse strength. Although suppressor of cytokine signalling 2 (SOCS2) is primarily known to negatively regulate cytokine signalling, it is also highly expressed in the hippocampus and exerts neuron-specific functions in the brain, effecting the length and architecture of neurons. However, little is known about the role of SOCS2 in the hippocampus. In this study, we hypothesised that SOCS2 may have a regulatory role in BDNF-dependent neurite growth and hippocampal neuronal function. Here our data demonstrate that SOCS2 interacts with the kinase domain of the BDNF receptor TrkB. Germline overexpression of SOCS2 results in a BDNF-dependent increase in hippocampal neurite outgrowth, whereas deletion of SOCS2 results in shorter neurite outgrowth. Expression of SOCS2 also results in increased ubiquitination of the juxtamembrane region of TrkB, and alters the trafficking of TrkB into recycling endosomes. Collectively, our data suggest a novel role for SOCS2 in interacting with and regulating the trafficking of TrkB, leading to increased neurite outgrowth in hippocampus neurons.",
keywords = "BDNF, Endosome trafficking, SOCS2, TrkB, Ubiquitination",
author = "Akram Zamani and Junhua Xiao and Turnley, {Ann M.} and Murray, {Simon S.}",
year = "2019",
month = "2",
day = "1",
doi = "10.1007/s12035-018-1168-8",
language = "English",
volume = "56",
pages = "1262--1275",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Springer-Verlag London Ltd.",
number = "2",

}

Tropomyosin-Related Kinase B (TrkB) Regulates Neurite Outgrowth via a Novel Interaction with Suppressor of Cytokine Signalling 2 (SOCS2). / Zamani, Akram; Xiao, Junhua; Turnley, Ann M.; Murray, Simon S.

In: Molecular Neurobiology, Vol. 56, No. 2, 01.02.2019, p. 1262-1275.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Tropomyosin-Related Kinase B (TrkB) Regulates Neurite Outgrowth via a Novel Interaction with Suppressor of Cytokine Signalling 2 (SOCS2)

AU - Zamani, Akram

AU - Xiao, Junhua

AU - Turnley, Ann M.

AU - Murray, Simon S.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Brain-derived neurotrophic factor (BDNF) is highly expressed in the hippocampus, where it can initiate signalling pathways leading to neurite outgrowth, neuron survival, spine maturation and increased synapse strength. Although suppressor of cytokine signalling 2 (SOCS2) is primarily known to negatively regulate cytokine signalling, it is also highly expressed in the hippocampus and exerts neuron-specific functions in the brain, effecting the length and architecture of neurons. However, little is known about the role of SOCS2 in the hippocampus. In this study, we hypothesised that SOCS2 may have a regulatory role in BDNF-dependent neurite growth and hippocampal neuronal function. Here our data demonstrate that SOCS2 interacts with the kinase domain of the BDNF receptor TrkB. Germline overexpression of SOCS2 results in a BDNF-dependent increase in hippocampal neurite outgrowth, whereas deletion of SOCS2 results in shorter neurite outgrowth. Expression of SOCS2 also results in increased ubiquitination of the juxtamembrane region of TrkB, and alters the trafficking of TrkB into recycling endosomes. Collectively, our data suggest a novel role for SOCS2 in interacting with and regulating the trafficking of TrkB, leading to increased neurite outgrowth in hippocampus neurons.

AB - Brain-derived neurotrophic factor (BDNF) is highly expressed in the hippocampus, where it can initiate signalling pathways leading to neurite outgrowth, neuron survival, spine maturation and increased synapse strength. Although suppressor of cytokine signalling 2 (SOCS2) is primarily known to negatively regulate cytokine signalling, it is also highly expressed in the hippocampus and exerts neuron-specific functions in the brain, effecting the length and architecture of neurons. However, little is known about the role of SOCS2 in the hippocampus. In this study, we hypothesised that SOCS2 may have a regulatory role in BDNF-dependent neurite growth and hippocampal neuronal function. Here our data demonstrate that SOCS2 interacts with the kinase domain of the BDNF receptor TrkB. Germline overexpression of SOCS2 results in a BDNF-dependent increase in hippocampal neurite outgrowth, whereas deletion of SOCS2 results in shorter neurite outgrowth. Expression of SOCS2 also results in increased ubiquitination of the juxtamembrane region of TrkB, and alters the trafficking of TrkB into recycling endosomes. Collectively, our data suggest a novel role for SOCS2 in interacting with and regulating the trafficking of TrkB, leading to increased neurite outgrowth in hippocampus neurons.

KW - BDNF

KW - Endosome trafficking

KW - SOCS2

KW - TrkB

KW - Ubiquitination

UR - http://www.scopus.com/inward/record.url?scp=85048084360&partnerID=8YFLogxK

U2 - 10.1007/s12035-018-1168-8

DO - 10.1007/s12035-018-1168-8

M3 - Article

VL - 56

SP - 1262

EP - 1275

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

IS - 2

ER -