Cellular and Molecular Life Sciences

, Volume 69, Issue 11, pp 1755–1771

The role of endocytosis in activating and regulating signal transduction

Review

DOI: 10.1007/s00018-011-0877-1

Cite this article as:
Andersson, E.R. Cell. Mol. Life Sci. (2012) 69: 1755. doi:10.1007/s00018-011-0877-1

Abstract

Endocytosis is increasingly understood to play crucial roles in most signaling pathways, from determining which signaling components are activated, to how the signal is subsequently transduced and/or terminated. Whether a receptor-ligand complex is internalized via a clathrin-dependent or clathrin-independent endocytic route, and the complexes’ subsequent trafficking through specific endocytic compartments, to then be recycled or degraded, has profound effects on signaling output. This review discusses the roles of endocytosis in three markedly different signaling pathways: the Wnt, Notch, and Eph/Ephrin pathways. These offer fundamentally different signaling systems: (1) diffusible ligands inducing signaling in one cell, (2) membrane-tethered ligands inducing signaling in a contacting receptor cell, and (3) bi-directional receptor-ligand signaling in two contacting cells. In each of these systems, endocytosis controls signaling in fascinating ways, and comparison of their similarities and dissimilarities will help to expand our understanding of endocytic control of signal transduction across multiple signaling pathways.

Keywords

EndocytosisClathrinDynaminCaveolinPrimary ciliumSignalingWntNotchEphEphrinEGF

Abbreviations

ADAM

A disintegrin and metallo-protease

AP1/2

Adaptor protein one or two

Arf

ADP-ribosylation factor

Arp2/3

Actin-related protein 2/3

Cav1/2

Caveolin one or two

CCP

Clathrin-coated pit

CCV

Clathrin-coated vesicle

CDR

Circular dorsal ruffles (also known as waves)

CE

Convergent extension

CLASP

Clathrin-associated sorting proteins

CLIC-GEEC

Clathrin-independent carrier/GPI-anchored protein-enriched early endosomal compartment

CME

Clathrin-mediated endocytosis

CSL

CBF1/Suppressor of Hairless/LAG-1

Dll1/3/4

Delta-like one, three or four (Notch ligands)

Dsh/Dvl

Disheveled

EEA1

Early endosomal antigen one

EGF

Epidermal growth factor

EGFR

Epidermal growth factor receptor

Fc

Fragment crystallizable region (tail region of antibody)

Flot1/2

Flotillin one or two

GPI

Glycosylphosphatidylinositol

GTPase

Guanosine triphosphate hydrolase enzyme

Hek cells

Human embryonic kidney cells

HeLa cells

Cervical cancer cells from Henrietta Lacks

HGF

Hepatocyte growth factor

Jag1/2

Jagged one or two (Notch ligands)

LacZ

Beta-d-galactosidase

LDL

Low-denstity lipoprotein

Lef1

Lymphoid enhancer-binding factor 1

Lqf

Liquid facets (Drosophila epsin homolog)

NECD

Notch extracellular domain

NEXT

Notch extracellular truncation

NICD

Notch intracellular domain

N-WASP

Neural Wiskott-Aldrich syndrome protein (aka WASL, Wiskott-Aldrich syndrome-like)

PCP

Planar cell polarity

PDGF

Platelet-derived growth factor

PKC

Protein kinase C

PM

Plasma membrane

Ptc

Patched (Shh receptor)

Rab11

Rab-protein 11

Rac1

RAS-related C3 botulinum substrate 1

Rin1

Ras and Rab interactor one

Ror1/2

Receptor tyrosine kinase-like orphan receptor one or two

Ryk

Receptor-like tyrosine kinase

Shh

Sonic hedgehog

TCF

T-cell factor

TGF-β

Transforming growth factor beta

Vav2

Vav 2 guanine nucleotide exchange factor

Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Department of Cell and Molecular BiologyKarolinska InstituteStockholmSweden