Endocytic adaptors – social networking at the plasma membrane

Abstract

Receptor-mediated endocytosis is a dynamic process that is crucial for maintaining plasma membrane composition and controlling cell-signaling pathways. A variety of entry routes have evolved to ensure that the vast array of molecules on the cell surface can be differentially internalized by endocytosis. This diversity has extended to include a growing list of endocytic adaptor proteins, which are thought to initiate the internalization process. The key function of adaptors is to select the proteins that should be removed from the cell surface. Thus, they have a central role in defining the physiology of a cell. This has made the study of adaptor proteins a very active area of research that is ripe for exciting future discoveries. Here, we review recent work on how adaptors mediate endocytosis and address the following questions: what characteristics define an endocytic adaptor protein? What roles do these proteins fulfill in addition to selecting cargo and how might adaptors function in clathrin-independent endocytic pathways? Through the findings discussed in this Commentary, we hope to stimulate further characterization of known adaptors and expansion of the known repertoire by identification of new adaptors.

Regulation of ubiquitin-dependent cargo sorting by multiple endocytic adaptors at the plasma membrane

“…Endocytic adaptors play a key role in cargo selection (5,6,15,16,24). To investigate a potential role for components of the FEI complex in ubiquitin-dependent protein sorting in C. elegans, we used previously isolated strains containing deletion mutations in each gene (Fig.…”

“…However, clathrin does not engage substrates directly nor does it exhibit the ability to associate with membranes. Instead, recruitment of clathrin is mediated by specific adaptor proteins found on different organelles, which interact with cargoes and lipid bilayers (5). At the plasma membrane, several endocytic adaptors coordinately regulate clathrin accumulation.…”

AP-2-complex-mediated endocytosis of Drosophila Crumbs regulates polarity by antagonizing Stardust

“…To unravel in more detail the molecular mechanisms by which endocytosis regulates Crb levels, we analyzed the molecular and functional interaction between Crb and AP-2, a complex involved in clathrin-mediated endocytosis (Matsui and Kirchhausen, 1990;reviewed in Boehm and Bonifacino, 2001;Godlee and Kaksonen, 2013;Maldonado-Báez and Wendland, 2006;Reider and Wendland, 2011;Traub, 2009). The AP-2 complex comprises the large α and β2 subunits, the medium μ2 subunit and the small σ2 subunit.…”

New Regulators of Clathrin-Mediated Endocytosis Identified in Saccharomyces cerevisiae by Systematic Quantitative Fluorescence Microscopy

“…NDOCYTOSIS is essential for numerous cellular activities including nutrient uptake, regulation of signal transduction, and remodeling of the cell surface (Robertson et al 2009;McMahon and Boucrot 2011;Reider and Wendland 2011;Weinberg and Drubin 2012;Boettner et al 2012;Kirchhausen et al 2014;Merrifield and Kaksonen 2014). Clathrin-mediated endocytosis (CME) is a major endocytic pathway that collects cargo into a coated pit, invaginates and pinches off a vesicle, and transports the vesicle to endosomes.…”

“…Clathrin-mediated endocytosis (CME) is a major endocytic pathway that collects cargo into a coated pit, invaginates and pinches off a vesicle, and transports the vesicle to endosomes. This process is carried out by a complex cellular machinery involving approximately 50 proteins to date (Robertson et al 2009;McMahon and Boucrot 2011;Reider and Wendland 2011;Boettner et al 2012;Weinberg and Drubin 2012;Kirchhausen et al 2014;Merrifield and Kaksonen 2014). CME is highly conserved throughout evolution and proceeds through a well-choreographed sequence of events where most proteins are recruited from the cytosol at specific times (Kaksonen et al 2003;Kaksonen et al 2005;Idrissi et al 2012;Kukulski et al 2012).…”