Endocytosis and membrane receptor internalization implication of F-BAR protein Carom

Abstract

Endocytosis is a cellular process mostly responsible for membrane receptor internalization. Cell membrane receptors bind to their ligands and form a complex which can be internalized. We previously proposed that F-BAR protein initiates membrane curvature and mediates endocytosis via their binding partners. However, F-BAR protein partners involved in membrane receptor endocytosis and the regulatory mechanism remain unknown. In this study, we established a group of database mining strategies to explore mechanisms underlying receptor-related endocytosis. We identified 34 endocytic membrane receptors and 10 regulating proteins for vesicle formation in clathrin-dependent endocytosis (CDE), a major process of membrane receptor internalization. We found that F-BAR protein FCHSD2 (Carom) may facilitate endocytosis via 9 endocytic partners. Carom is highly expressed, along with highly expressed endocytic membrane receptors and partners, in endothelial cells and macrophages. We established 3 models of Carom-receptor complex and their intracellular trafficking based on protein-protein interaction and subcellular localization. We conclude that Carom may mediate receptor endocytosis and transport endocytic receptors to the cytoplasm for receptor signaling and lysosome/proteasome degradation, or to the nucleus for RNA processing, gene transcription and DNA repair. HHS Public Access INTRODUCTIONEndocytosis is a cellular process by which molecules or substances are transported into the cell via cell membrane engulfment. Endocytosis is generally classified as phagocytosis and pinocytosis, which are distinguished by the size of the endocytic vesicles formed ( Figure 1A & B) (1). Phagocytosis implies to the ingestion of large and solid particle (diameter 0.5-10μm) such as pathogens. Pinocytosis refers to internalization of various liquid via small endocytic vesicles and can be divided into four subtypes: macropinocytosis, clathrindependent, caveolae-dependent, and clathrin/caveolae-independent endocytosis based on clatherin or caveolae involvement (2). Pathogens or ligands induce endocytosis by binding to the cell membrane via receptor-dependent or -independent mechanisms, and then form phagosome or endocytic vesicle (Figure 1B & C). Endocytic vesicle may be coated with clathrin, caveolae or regulated by flotillin, Rho GTPase activating protein 26 (GRAF1), ADP-Ribosylation factor 6 (Arf6) and Ras homology family membrane A (RhoA). During phagocytosis, solid particle containing-phagosomes fuse with lysosomes (marked by lysosomal associated membrane protein (LAMP1)) and subjected to lysosomal degradation. In the process of pinocytosis, internalized vesicles are transported to early endosome (marked by Ras associated protein (Rab5)), which delivers the cargoes to three locations: 1) late endosome (marked by Ras associated protein (Rab7)) then lysosome for degradation, 2) recycling endosome (marked by Rab11) for signal transduction or receptor recycling to cell membrane, and 3) nucleus to regulate transcription factor and ch...

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