Biological Basket Weaving: Formation and Function of Clathrin-Coated Vesicles

Abstract

There has recently been considerable progress in understanding the regulation of clathrin-coated vesicle (CCV) formation and function. These advances are due to the determination of the structure of a number of CCV coat components at molecular resolution and the identification of novel regulatory proteins that control CCV formation in the cell. In addition, pathways of (a) phosphorylation, (b) receptor signaling, and (c) lipid modification that influence CCV formation, as well as the interaction between the cytoskeleton and CCV transport pathways are becoming better defined. It is evident that although clathrin coat assembly drives CCV formation, this fundamental reaction is modified by different regulatory proteins, depending on where CCVs are forming in the cell. This regulatory difference likely reflects the distinct biological roles of CCVs at the plasma membrane and trans-Golgi network, as well as the distinct properties of these membranes themselves. Tissue-specific functions of CCVs require even more-specialized regulation and defects in these pathways can now be correlated with human diseases.

Mutant Huntingtin Impairs Post-Golgi Trafficking to Lysosomes by Delocalizing Optineurin/Rab8 Complex from the Golgi Apparatus

“…Consistent with this result, Western blot analysis showed no differences in the levels of total ␥-adaptin protein between wt and mhtt cells, whereas the protein levels of ␥-adaptin in isolated Golgi membranes were significantly increased in mhtt cells ( Figure 7B). These findings suggest that clathrin-dependent post-Golgi trafficking is impaired, because AP-1 provides the first step of cargo-sequestration specificity in this route (Brodsky et al, 2001;McNiven and Thompson, 2006). Thus, we next examined the ultrastructure of the Golgi apparatus in wt and mhtt cells.…”

RAB-10 Is Required for Endocytic Recycling in theCaenorhabditis elegansIntestine

“…Endocytosis and endocytic trafficking controls the uptake and sorting of extracellular macromolecules as well as the components of the cell membrane itself, counterbalancing secretion and allowing a complex interplay between cells and their environment that is important for a myriad of cellular activities (Brodsky et al, 2001;Maxfield and McGraw, 2004). The steps involved in the uptake and trafficking of cargo within the endosomal system have been well described, but many of the components mediating these steps at the molecular level remain to be identified (Brodsky et al, 2001;Maxfield and McGraw, 2004).…”

“…The steps involved in the uptake and trafficking of cargo within the endosomal system have been well described, but many of the components mediating these steps at the molecular level remain to be identified (Brodsky et al, 2001;Maxfield and McGraw, 2004). Many receptors and their associated ligands cluster into clathrincoated pits, whereas other types of cargo utilize clathrinindependent uptake mechanisms (Nichols, 2003;Gesbert et al, 2004).…”

Clathrin-dependent Association of CVAK104 with Endosomes and theTrans-Golgi Network

“…Clathrin-coated vesicles (CCVs) are intracellular transport carriers that deliver cargo from the plasma membrane and the trans-Golgi network (TGN) to the endosomal compartment (Brodsky et al, 2001). The first stage in CCV formation involves the assembly of clathrin molecules into a polygonal lattice at the cytoplasmic face of the donor membrane and the formation of a clathrin-coated bud.…”