Spoiled for Choice: Diverse Endocytic Pathways Function at the Cell Surface - PubMed (original) (raw)

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Spoiled for Choice: Diverse Endocytic Pathways Function at the Cell Surface

Joseph Jose Thottacherry et al. Annu Rev Cell Dev Biol. 2019.

Abstract

Endocytosis has long been identified as a key cellular process involved in bringing in nutrients, in clearing cellular debris in tissue, in the regulation of signaling, and in maintaining cell membrane compositional homeostasis. While clathrin-mediated endocytosis has been most extensively studied, a number of clathrin-independent endocytic pathways are continuing to be delineated. Here we provide a current survey of the different types of endocytic pathways available at the cell surface and discuss a new classification and plausible molecular mechanisms for some of the less characterized pathways. Along with an evolutionary perspective of the origins of some of these pathways, we provide an appreciation of the distinct roles that these pathways play in various aspects of cellular physiology, including the control of signaling and membrane tension.

Keywords: CLIC/GEEC; caveolae; clathrin-independent endocytosis; clathrin-mediated endocytosis; dynamin; evolution; signaling.

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Figures

Figure 1

Figure 1. Different endocytic pathways and their itinerary

Multiple clathrin independent endocytic pathways function at the cell surface. These can be divided based on their requirement for clathrin (brown, orange) or dynamin (green, purple) dependence. Some pathways are not constitutively active and are marked as induced. Cargoes for these pathways are listed in Supplementary Table S1. Endosomes formed from each of the dynamin-dependent pathways fuse with the sorting endosome from which material is sorted to recycling endosome. The sorting endosome matures to late endosomes which subsequently fuse with lysosome. Dynamin-independent pathways give rise to CLICs which fuse to form GEECs. GEECS also deliver some of their contents to the sorting endosome, but independently recycle content bypassing the sorting and recycling endosome. There are clathrin and dynamin independent pathways based on cargo (see Supplementary Table S1) which remain unclassified and are denoted as other (these are noted in the section - Types of endocytosis).

Figure 2

Figure 2. Steps in endocytosis

The process is initiated with cargo selection and their recruitment to the forming endocytic site/pit. The cargo can come from the extracellular milieu or belong to the plasma membrane. Once selected, generation of a budding vesicle connected with the plasma membrane occurs by assembling proteins, which help with the bending and stabilization of the bud (Step 1). These proteins can be coat proteins such as clathrin/caveolin or curvature sensing/stabilization proteins. Regardless of the exact machinery used, it leads to the formation of an endocytic pit/invagination, which is, over time, sculpted to make a neck. The neck is constricted and eventually cut to release the endocytic vesicle inside the cell by a process of vesicle scission (Step 2). Here, most endocytic pathway deploys either dynamin alone (Step 2a) or dynamin in conjugation with actin or motor proteins (Step 2b). There are a class of processes that neither utilizes coat proteins nor requires dynamin for scission (Step 2c). These budding vesicles are then pinched to release an endocytic vesicle into the cell (Step 3).

Figure 3

Figure 3. Timeline of key findings showing contrast between the study of CME and CIE.

The time line shows key findings in different endocytic pathways. EM based observations picked up clathrin dependent pathways due to the presence of electron dense coat (1964). It took another decade before clathrin was isolated. Existence of a clathrin independent pathway was hinted from observations where Thy1 (GPI-AP) was found excluded from coated pits (1980) and later the fluid-phase and ricin toxin were endocytosed even when clathrin mediated endocytosis was inhibited (1986/87). These molecules are now internalized via multiple clathrin and dynamin-independent mechanisms (1995/1997/2002). Clathrin independent pathways are still being discovered with the RhoA-dependent FEME being the most recent addition (2001/2015). Important milestones in the discovery of multiple endocytic pathways: a - (Palade & GE 1953, Yamada 1955), b- (Roth & Porter 1964), c- (Pearse 1975, 1976), d- (Anderson et al. 1977a,b), e- (Bretscher et al. 1980), f - (Kosaka & Ikeda 1983), g- (Moya et al. 1985, Sandvig 1987), h- (Bar-Sagi & Feramisco 1986), i - (Jackson et al. 1987; Kirchhausen et al. 1987a,b), j- (Robinson 1989, Thurieau et al. 1988), k-(Rothberg et al. 1992, Scherer et al. 1996, Tang et al. 1996), l- (Damke et al. 1994), m- (Damke et al. 1994, 1995), n- (Radhakrishna & Donaldson 1997), o- (Lamaze et al. 2001), p- (Sabharanjak et al. 2002), q- (Aboulaich et al. 2004, Hill et al. 2008), r-(Frick et al. 2007, Glebov et al. 2006) s- (Gupta et al. 2009, Kumari & Mayor 2008), t- (Boucrot et al. 2015, Renard et al. 2015), u- (Sathe et al. 2018).

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