Review series: From uncertain beginnings: initiation mechanisms of clathrin-mediated endocytosis - PubMed (original) (raw)

Review

Review series: From uncertain beginnings: initiation mechanisms of clathrin-mediated endocytosis

Camilla Godlee et al. J Cell Biol. 2013.

Abstract

Clathrin-mediated endocytosis is a central and well-studied trafficking process in eukaryotic cells. How this process is initiated is likely to be a critical point in regulating endocytic activity spatially and temporally, but the underlying mechanisms are poorly understood. During the early stages of endocytosis three components-adaptor and accessory proteins, cargo, and lipids-come together at the plasma membrane to begin the formation of clathrin-coated vesicles. Although different models have been proposed, there is still no clear picture of how these three components cooperate to initiate endocytosis, which may indicate that there is some flexibility underlying this important event.

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Figures

Figure 1.

Figure 1.

Examples of regulation of the initiation of endocytosis. (A) In yeast Saccharomyces cerevisiae, clathrin-mediated endocytosis is polarized to the growing bud. (B) After signal propagation at the synapse, exocytosis of the neurotransmitter is accompanied by a compensatory increase in clathrin-mediated endocytosis to maintain synaptic plasma membrane area and recycle synaptic vesicle components. (C) Many viruses enter the host cell by clathrin-mediated endocytosis. The virus particle may exploit the cell’s regulation of endocytosis in order to induce its own uptake.

Figure 2.

Figure 2.

The key players involved in the initiation of endocytosis. Adaptor proteins, cargo, lipids, and clathrin accumulate at the plasma membrane to make up the nascent endocytic site. Adaptor proteins, including the AP2 complex, bind to the inner leaflet of the plasma membrane. The adaptors interact with the plasma membrane via lipid-binding domains, many of which bind specifically to PIP2. The tails of adaptor proteins bind and recruit clathrin triskelions to the plasma membrane where they polymerize to form the clathrin coat. Cargo—consisting of transmembrane receptors and extracellular soluble ligands—is taken up by clathrin-coated vesicles. Adaptors bind to signaling motifs on the intracellular side of the receptors.

Figure 3.

Figure 3.

Possible mechanisms for the initiation of endocytosis. (A) Stochastic interactions of adaptors and lipids at the plasma membrane can form a nucleus that recruits further endocytic components. One such assembly that has been proposed is two AP2 complexes along with a clathrin triskelion (Cocucci et al., 2012). (B) Membrane bending may be required or aid in the initiation of endocytosis. Protein domains such as the F-BAR domain have been suggested to induce membrane bending as a mechanism for initiating endocytic site formation (Henne et al., 2010). (C) Clustering of cargo molecules has been shown to be able to induce the assembly of endocytic components de novo (Liu et al., 2010). (D) Specific lipids forming a lipid gradient or at a membrane domain could increase the recruitment of adaptors to the plasma membrane, leading to increased initiation of endocytosis.

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References

    1. Abe N., Inoue T., Galvez T., Klein L., Meyer T. 2008. Dissecting the role of PtdIns(4,5)P2 in endocytosis and recycling of the transferrin receptor. J. Cell Sci. 121:1488–1494 10.1242/jcs.020792 - DOI - PMC - PubMed
    1. Aguet F., Antonescu C.N., Mettlen M., Schmid S.L., Danuser G. 2013. Advances in analysis of low signal-to-noise images link dynamin and AP2 to the functions of an endocytic checkpoint. Dev. Cell. 26:279–291 10.1016/j.devcel.2013.06.019 - DOI - PMC - PubMed
    1. Antonescu C.N., Danuser G., Schmid S.L. 2010. Phosphatidic acid plays a regulatory role in clathrin-mediated endocytosis. Mol. Biol. Cell. 21:2944–2952 10.1091/mbc.E10-05-0421 - DOI - PMC - PubMed
    1. Antonescu C.N., Aguet F., Danuser G., Schmid S.L. 2011. Phosphatidylinositol-(4,5)-bisphosphate regulates clathrin-coated pit initiation, stabilization, and size. Mol. Biol. Cell. 22:2588–2600 10.1091/mbc.E11-04-0362 - DOI - PMC - PubMed
    1. Beattie E.C., Howe C.L., Wilde A., Brodsky F.M., Mobley W.C. 2000. NGF signals through TrkA to increase clathrin at the plasma membrane and enhance clathrin-mediated membrane trafficking. J. Neurosci. 20:7325–7333 - PMC - PubMed

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