Endocytic membrane trafficking involves the cellular internalization and sorting of extracellular molecules, plasma membrane proteins and lipids. Endocytosis is required for a vast number of functions, including nutrient uptake, cell adhesion and migration, receptor signalling, pathogen entry and cell polarity. It is well established that endocytosis regulates receptor-mediated signalling (including signalling from receptor tyrosine kinases and G protein-coupled receptors). Conversely, it is becoming apparent that signalling events regulate the endocytic pathway — illustrating how these molecular networks are intertwined (see the Review by Sorkin and von Zastrow).

Different types of endocytic processes can be distinguished by the size of the vesicle formed, their cargo and the machineries involved. Endocytosis that is mediated by vesicles coated with clathrin is the best characterized pathway, yet the selection of cargo by adaptor proteins is considerably more complex than initially anticipated (see the Review by Traub). In recent years, non-clathrin-mediated pathways, including macropinocytosis, phagocytosis and caveolin-dependent pathways, have gained considerable interest, which in turn has led to the discovery of new endocytic recycling systems (see the Review by Grant and Donaldson). Further down the endocytic pathway, lysosomes are the primary catabolic compartments of eukaryotic cells that degrade extracellular material internalized via endocytosis and intracellular components sequestered by autophagy. The importance of lysosomal trafficking pathways is emphasized by recent findings describing new roles of lysosomal membrane proteins in cellular physiology and an increasing number of diseases that is recognized as a defect in lysosome biogenesis. (see the Review by Saftig and Klumperman).

This special Focus on endocytosis reflects the diversity and complexity of endocytic trafficking processes and their associated machineries, as exemplified by the four Reviews. The Nature Research library contains other relevant articles, including Reviews, on the broad topic of endocytosis.

Research Highlights

In brief

Endocytosis | Endocytosis | Endocytosis | PDF (118 KB)

p579 | doi:10.1038/nrm2756

Nature Reviews Molecular Cell Biology 10, 579

Endocytosis: Joint efforts of ESCRTs


Nature Reviews Molecular Cell Biology 10, 581

Journal Club

Seeing is believing | PDF (134 KB)

p582 | doi:10.1038/nrm2747

Nature Reviews Molecular Cell Biology 10, 582



Molecular mechanism and physiological functions of clathrin-mediated endocytosis

Harvey T. McMahon & Emmanuel Boucrot


Nature Reviews Molecular Cell Biology 12, 517-533 (2011)

Clathrin-mediated endocytosis is a modular process that involves core and accessory adaptor proteins that package cargoes into vesicles, ultimately leading to their uptake. It is essential for many physiological processes in higher eukaryotes, including signal termination and exocytosis, so its components are rarely associated with disease.

ARF family G proteins and their regulators: roles in membrane transport, development and disease

Julie G. Donaldson & Catherine L. Jackson


Nature Reviews Molecular Cell Biology 12, 362-375 (2011)

The ADP-ribosylation factor (ARF) and ARF-like (ARL) family of G proteins, which are known to regulate membrane traffic and organelle structure, are emerging as regulators of diverse processes, including lipid and cytoskeletal transport. Although traditionally viewed as part of a linear signalling pathway, ARFs and their regulators must now be considered to exist within functional networks, in which both the 'inactive' ARF and the regulators themselves can mediate distinct effects.

Membrane budding and scission by the ESCRT machinery: it's all in the neck

James H. Hurley & Phyllis I. Hanson


Nature Reviews Molecular Cell Biology 11, 556-566 (2010)

The endosomal sorting complex required for transport (ESCRT) machinery catalyses membrane budding in the endolysosomal pathway, which differs from other budding events in that it is directed away from the cytosol. Recent studies have elucidated a mechanism whereby ESCRT-I and ESCRT-II stabilize the bud neck and ESCRT-III mediates neck cleavage.

Tickets to ride: selecting cargo for clathrin-regulated internalization

Linton M. Traub


Nature Reviews Molecular Cell Biology 10, 583-596 (2009)

Clathrin-mediated endocytosis dynamically regulates the composition of the plasma membrane in eukaryotic cells by internalizing transmembrane proteins, bound ligands and lipids. To regulate the uptake of a vast array of cargo molecules, specific sorting signals in cargoes are decoded by different cytosolic adaptor proteins.

Pathways and mechanisms of endocytic recycling

Barth D. Grant & Julie G. Donaldson


Nature Reviews Molecular Cell Biology 10, 597-608 (2009)

Studies of cargo proteins that are internalized independently of clathrin have revealed new pathways and mechanisms of endocytic recycling. Precise temporal and spatial regulation of recycling pathways is crucial for various cellular processes, including cytokinesis, cell adhesion, morphogenesis, cell fusion, learning and memory.

Endocytosis and signalling: intertwining molecular networks

Alexander Sorkin & Mark von Zastrow


Nature Reviews Molecular Cell Biology 10, 609-622 (2009)

It is now recognized that cell signalling and endocytic membrane trafficking are intimately and bidirectionally linked in animal cells. The mechanistic and functional principles that underlie the relationship between these cellular processes are becoming increasingly evident across many systems.

Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function

Paul Saftig & Judith Klumperman


Nature Reviews Molecular Cell Biology 10, 623-635 (2009)

Lysosomes are the primary catabolic compartments of eukaryotic cells. They degrade extracellular material that has been internalized by endocytosis and intracellular components that have been sequestered by autophagy. Emerging evidence suggests that there are multiple lysosomal delivery pathways that together allow the regulated and sequential deposition of lysosomal components.


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