Elsevier

Cytokine & Growth Factor Reviews

Volume 32, December 2016, Pages 63-73
Cytokine & Growth Factor Reviews

Mini review
Endocytic regulation of cytokine receptor signaling

https://doi.org/10.1016/j.cytogfr.2016.07.002Get rights and content
Under a Creative Commons license
open access

Highlights

  • Endocytosis regulates signaling of plasma membrane receptors.

  • Cytokine receptors can be internalized by various mechanisms.

  • Cytokine receptors can use endosomes as signaling platforms.

  • The effects of endocytosis on signaling output are known for a few cytokine receptors.

Abstract

Signaling of plasma membrane receptors can be regulated by endocytosis at different levels, including receptor internalization, endocytic sorting towards degradation or recycling, and using endosomes as mobile signaling platforms. Increasing number of reports underscore the importance of endocytic mechanisms for signaling of cytokine receptors. In this short review we present both consistent and conflicting data regarding endocytosis and its role in signaling of receptors from the tumor necrosis factor receptor superfamily (TNFRSF) and those for interleukins (ILRs) and interferons (IFNRs). These receptors can be internalized through various endocytic routes and most of them are able to activate downstream pathways from endosomal compartments. Moreover, some of the cytokine receptors clearly require endocytosis for proper signal transduction. Still, the data describing internalization mechanisms and fate of cytokine receptors are often fragmentary and barely address the relation between their endocytosis and signaling. In the light of growing knowledge regarding different mechanisms of endocytosis, extending it to the regulation of cytokine receptor signaling may improve our understanding of the complex and pleiotropic functions of these molecules.

Abbreviations

CIE
clathrin-independent endocytosis
CME
clathrin-mediated endocytosis
DRM
detergent-resistant microdomains
EGFR
epidermal growth factor receptor
GPI-AP
glycosylphosphatidylinositol-anchored proteins
IFN
interferon
IFNAR
type I interferon receptor
IFNGR
type II interferon receptor
IFNR
interferon receptor
IL
interleukin
ILR
interleukin receptor
ILV
intraluminal vesicle
JNK
c-Jun N-terminal kinase
LTβR
lymphotoxin β receptor
MVB
multivesicular body
MβCD
methyl-β-cyclodextrin
PI3K
phosphoinositide 3-kinase
RTK
receptor tyrosine kinase
TNF
tumor necrosis factor
TNFRSF
tumor necrosis factor receptor superfamily

Keywords

Internalization
Endocytosis
Trafficking
Endosome
Multivesicular body
Clathrin
Dynamin
Cytokine receptor
TNF
Interleukin
Interferon
Lymphotoxin
Signaling
NF-κB
Jak
STAT

Cited by (0)

Jaroslaw Cendrowski received his PhD in Biochemistry, Molecular Biology and Biomedicine from Autonomous University of Madrid in 2013. He carried out the PhD project at the Spanish National Cancer Research Centre (CNIO) in Madrid, Spain under the supervision of Francisco X. Real. Currently, he works as a postdoctoral fellow at the International Institute of Molecular and Cell Biology in Warsaw in the laboratory of Marta Miaczynska. His research interests include the role of endocytosis in regulation of intracellular signaling in the context of inflammation, cancer and development.

Agnieszka Mamińska obtained her PhD in Cell Biology with distinction in 2015, after performing the doctoral project in the International Institute of Molecular and Cell Biology in Warsaw in the laboratory of Marta Miaczynska. She is currently a postdoctoral fellow in the same group. She carried out laboratory trainings at the University of Glasgow (UK), University of Chicago (USA) and University of Oslo (Norway). Her scientific interests include interplay of endocytosis with signal transduction, mechanisms of receptor trafficking in the cell and role of membrane transport in host-pathogen interactions.

Marta Miaczynska is head of the Laboratory of Cell Biology at the International Institute of Molecular and Cell Biology in Warsaw since 2005 and a full professor since 2013. She received her PhD in genetics in 1997 from Vienna University and did postdoctoral work at the European Molecular Biology Laboratory in Heidelberg and at the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden. She has received numerous fellowships and grants, such as Human Frontier Science Program Organization fellowship, Wellcome Trust Senior Research Fellowship (UK), International Scholar of the Howard Hughes Medical Institute (USA), L’Oreal Poland fellowship for Women in Science, MAESTRO grant from the National Science Center or a grant from the Polish-Swiss Research Programme. Her research interests have focused on the molecular mechanisms integrating membrane transport with signal transduction in the cell, in particular the biogenesis of endosomes and their functions in signaling.

1

These authors contributed equally to this work.