Cellular and Molecular Life Sciences

, Volume 69, Issue 11, pp 1755–1771 | Cite as

The role of endocytosis in activating and regulating signal transduction

  • Emma R. AnderssonEmail author


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.


Endocytosis Clathrin Dynamin Caveolin Primary cilium Signaling Wnt Notch Eph Ephrin EGF 



A disintegrin and metallo-protease


Adaptor protein one or two


ADP-ribosylation factor


Actin-related protein 2/3


Caveolin one or two


Clathrin-coated pit


Clathrin-coated vesicle


Circular dorsal ruffles (also known as waves)


Convergent extension


Clathrin-associated sorting proteins


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


Clathrin-mediated endocytosis


CBF1/Suppressor of Hairless/LAG-1


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




Early endosomal antigen one


Epidermal growth factor


Epidermal growth factor receptor


Fragment crystallizable region (tail region of antibody)


Flotillin one or two




Guanosine triphosphate hydrolase enzyme

Hek cells

Human embryonic kidney cells

HeLa cells

Cervical cancer cells from Henrietta Lacks


Hepatocyte growth factor


Jagged one or two (Notch ligands)




Low-denstity lipoprotein


Lymphoid enhancer-binding factor 1


Liquid facets (Drosophila epsin homolog)


Notch extracellular domain


Notch extracellular truncation


Notch intracellular domain


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


Planar cell polarity


Platelet-derived growth factor


Protein kinase C


Plasma membrane


Patched (Shh receptor)


Rab-protein 11


RAS-related C3 botulinum substrate 1


Ras and Rab interactor one


Receptor tyrosine kinase-like orphan receptor one or two


Receptor-like tyrosine kinase


Sonic hedgehog


T-cell factor


Transforming growth factor beta


Vav 2 guanine nucleotide exchange factor



E.R.A. thanks Professor Urban Lendahl for scientific discussions and support, and Dr. Nicolas Fritz for fruitful discussions and constructive criticism of the manuscript.


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© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Department of Cell and Molecular BiologyKarolinska InstituteStockholmSweden

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