Journal Article

Pathways of clathrin-independent endocytosis

Mayor, Satyajit, Pagano, Richard E.

2007

Overview

Key Points In addition to the classical clathrin-dependent mechanisms of endocytosis, there are several pathways that do not use a clathrin coat and are, therefore, referred to as clathrin-independent (CI) mechanisms. CI mechanisms of uptake have gained much attention with the realization that they have important roles in the regulation of cell growth and development as well as important implications in the study of certain diseases and pathogens. Two well-known CI mechanisms are the caveolar pathway and fluid-phase endocytosis. However, there is much debate concerning the number of distinct CI mechanisms that exist, the best cargo molecules for the study of a particular pathway, and the underlying protein machinery that regulates these pathways. To organize the extensive literature on CI endocytosis for the purpose of arriving at a mechanistic understanding, this Review classifies CI mechanisms as follows: first, on whether or not they are dynamin dependent and, second, according to the involvement of the small GTPases CDC42, RhoA or ARF6. Protein-based mechanisms (for example, ubiquitylation) and lipid-based mechanisms (for example, nanoscale clustering of lipid-tethered proteins) may both function in the selection of cargo for CI endocytosis. The mechanism of budding in the dynamin-independent pathways remains elusive; however, recent theoretical studies provide testable ideas in this area. Classically, endocytosis involves the formation of clathrin-coated carriers that bud from the plasma membrane by dynamin-dependent mechanisms. Recently, several clathrin-independent endocytic pathways have been identified, which represent the main pathway of entry into cells for a diverse array of cargoes, including receptors, lipids and pathogens. There are numerous ways that endocytic cargo molecules may be internalized from the surface of eukaryotic cells. In addition to the classical clathrin-dependent mechanism of endocytosis, several pathways that do not use a clathrin coat are emerging. These pathways transport a diverse array of cargoes and are sometimes hijacked by bacteria and viruses to gain access to the host cell. Here, we review our current understanding of various clathrin-independent mechanisms of endocytosis and propose a classification scheme to help organize the data in this complex and evolving field.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Animals / Bacteria - metabolism / Bacteria - ultrastructure / Biochemistry / Biological Transport, Active / Biology / Biomedical and Life Sciences / Cancer Research / Cell Biology / Cell metabolism / Classification schemes / Clathrin / Developmental Biology / Endocytosis / Eukaryotic Cells - metabolism / Eukaryotic Cells - microbiology / Eukaryotic Cells - ultrastructure / Eukaryotic Cells - virology / Humans / Life Sciences / Physiological aspects / Plasma / Proteins / review-article / Stem Cells / Virus Internalization / Viruses - metabolism / Viruses - ultrastructure