Endocytic Accessory Factors and Regulation of Clathrin-Mediated Endocytosis

Up to 60 different proteins are recruited to the site of clathrin-mediated endocytosis in an ordered sequence. These accessory proteins have roles during all the different stages of clathrin-mediated endocytosis. First, they participate in the initiation of the endocytic event, thereby determining when and where endocytic vesicles are made; later they are involved in the maturation of the clathrin coat, recruitment of specific cargo molecules, bending of the membrane, and finally in scission and uncoating of the nascent vesicle. In addition, many of the accessory components are involved in regulating and coupling the actin cytoskeleton to the endocytic membrane. We will discuss the different accessory components and their various roles. Most of the data comes from studies performed with cultured mammalian cells or yeast cells. The process of endocytosis is well conserved between these different organisms, but there are also many interesting differences that may shed light on the mechanistic principles of endocytosis.Receptor-mediated endocytosis is the process by which eukaryotic cells concentrate and internalize cell surface receptors from the plasma membrane into small (∼50 nm– ∼100 nm diameter) membrane vesicles (Chen et al. 2011; McMahon and Boucrot 2011; Weinberg and Drubin 2012). This mechanism has been studied extensively in mammalian tissue culture cells and in yeast, and despite the evolutionary distance between yeast and mammalian cells the mechanism of receptor-mediated endocytosis in the respective cell types show remarkable similarities. Indeed many of the ∼60 endocytic accessory proteins (EAPs) found in yeast have homologs in mammalian cells, although both cell types also have unique EAPs (McMahon and Boucrot 2011; Weinberg and Drubin 2012).In the following, we briefly describe known yeast and mammalian EAPs (Sigismund et al. 2012; see also Bökel and Brand 2013; Cosker and Segal 2014; Di Fiore and von Zastrow 2014).

Table 1.

Key endocytic proteins in mammals and in yeast

	Mammals	Yeast	Function
Coat proteins	Clathrin	Chc1, Clc1	Coat protein
	AP-2 (4 subunits)	AP-2 (4 subunits)	Adaptor protein
	Epsin	Ent1/2	Adaptor protein
	AP180	Yap1801/2	Adaptor protein
	CALM	–	Adaptor protein
	NECAP	–	Adaptor protein
	FCHo1/2	Syp1	Adaptor protein
	Eps15	Ede1	Scaffold protein
	Intersectin	Pan1	Scaffold protein
	–	Sla1	Scaffold protein
	–	End3	Scaffold protein
N-BAR proteins	Amphiphysin	Rvs161/167	Membrane curvature sensor/generator
	Endophilin	–	Membrane curvature sensor/generator
	BIN1	–	Membrane curvature sensor/generator
Dynamin	Dynamin1/2	Vps1	Mechanoenzyme, GTPase
Actin cytoskeleton	Actin	Act1	Actin monomer
	Arp2/3 complex	Arp2/3 complex	Actin filament nucleator
	ABP1	Abp1	Actin-binding protein
	Cortactin	–	Actin-binding protein
	Coronin	Crn1	Actin-binding protein
	Cofilin	Cof1	Actin depolymerizing protein
Actin regulators	Myosin 1E	Myo3/5	Actin motor
	Myosin 6		Actin motor
	Hip1R, Hip1	Sla2	Actin-membrane coupler
	Syndapin	Bzz1	BAR domain protein
	N-WASP	Las17	Regulator of actin nucleation
	WIP/WIRE	Vrp1	Regulator of actin nucleation
	SNX9	–	Regulator of actin nucleation
	–	Bbc1	Regulator of actin nucleation
Other regulators	AAK1	Ark1/Prk1	Protein kinase
	Auxilin, GAK	–	Uncoating factor
	Synaptojanin	Sjl2	Lipid phosphatase
	OCRL1	–	Lipid phosphatase

Open in a separate windowThe proteins are grouped into functional categories and the homologous proteins are listed on the same line.