Clathrin-Independent Pathways of Endocytosis

Abstract

There are many pathways of endocytosis at the cell surface that apparently operate at the same time. With the advent of new molecular genetic and imaging tools, an understanding of the different ways by which a cell may endocytose cargo is increasing by leaps and bounds. In this review we explore pathways of endocytosis that occur in the absence of clathrin. These are referred to as clathrin-independent endocytosis (CIE). Here we primarily focus on those pathways that function at the small scale in which some have distinct coats (caveolae) and others function in the absence of specific coated intermediates. We follow the trafficking itineraries of the material endocytosed by these pathways and finally discuss the functional roles that these pathways play in cell and tissue physiology. It is likely that these pathways will play key roles in the regulation of plasma membrane area and tension and also control the availability of membrane during cell migration.

Endocytosis and Cancer

“…CCVs perform this task by decoding specific recognition sequences found on the cytoplasmic domains of many receptors or interacting with posttranslational modifications such as ubiquitination, acetylation (Goh et al 2010), or lysine methylation of the internalizing receptor (Hsu et al 2011). Other types of endocytic vesicles can also form notably small vesicles that lack clathrin coats, some of which are derived from plasma membrane "caveolae" that contain defined-lipid microdomains that are involved in a variety of signal transduction events (e.g., GPI-anchored proteins and some G-proteincoupled receptors) (see Mayor et al 2014). Larger vesicles, called "macropinosomes," can also form in many cell types with macropinocytosis occurring either constitutively in some examples or by induced receptor stimulation or bacterial entry in others; typically, macropinocytosis reflects local activation of Cdc42 (Garrett et al 2000).…”

Lipid Sorting and Multivesicular Endosome Biogenesis

“…Animal cells take up solutes, nutrients, ligands, and components of the plasma membrane via multiple endocytic pathways, which all merge in common early endosomes (Mayor and Pagano 2007;Doherty and McMahon 2009;Donaldson et al 2013;Johannes et al 2013;Kirchhausen et al 2013;Merrifield and Kaksonen 2013). There, cargo can be sorted to different cellular destinations, including the plasma membrane, the trans-Golgi network (TGN), or late endosomes.…”

Endocytosis: Past, Present, and Future

“…We begin with several articles that describe our current understanding of the molecular machinery and mechanisms driving entry of cargo (e.g., receptors and bound ligands) into the cell, by clathrin-dependent and -independent endocytosis (Traub and Bonifacino 2013;Kirchhausen et al 2014;Mayor et al 2014;Merrifield and Kaksonen 2014;Mettlen and Danuser 2014). Following internalization, the endocytosed material is shuttled along an ultrastructurally complex and dynamic pathway of tubular and vesicular compartments collectively known as endosomes, and described in the article by Klumperman and Raposo (2014), from which they can be sorted for recycling back to the cell surface or delivered to lysosomes for degradation.…”