Analysis for Carom complex signaling and function by database mining

Liu, Suxuan; Xiong, Xinyu; Thomas, Sam; Xu, Yanjie; Cheng, Xiaoshu; Zhao, Xianxian; Yang, Xiaofeng; Wang, Hong

doi:10.2741/4424

Cited by 6 publications

(1 citation statement)

References 45 publications

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“…It interacts with proline-rich proteins, such as adaptor and signaling proteins, via its C-terminal SH3 domains to form a functional complex at cellular membranes. Based on their endocytosis-related function reported in the literature, we selected 9 proteins from 26 Carom partners we previously identified, and termed them as Carom endocytic partners (Table 3) (32). It was reported that these Carom endocytic partners played important role in regulating actin polymerization, endocytic vesicle formation and protein ubiquitination.…”

Section: Resultsmentioning

confidence: 99%

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

Xia

Liu

et al. 2017

Front Biosci

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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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Section: Resultsmentioning

confidence: 99%

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

Xia

Liu

et al. 2017

Front Biosci

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Cardiovascular Disease Risk Factors, Immune Checkpoints and Tregs

Shao,

Saaoud,

et al. 2024

Advances in Biochemistry in Health and Disease

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Role for ERK1/2-dependent activation of FCHSD2 in cancer cell-selective regulation of clathrin-mediated endocytosis

Xiao

Mohanakrishnan

Schmid

2018

Proc. Natl. Acad. Sci. U.S.A.

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Clathrin-mediated endocytosis (CME) regulates the uptake of cell-surface receptors as well as their downstream signaling activities. We recently reported that signaling can reciprocally regulate CME in cancer cells and that this crosstalk can contribute to cancer progression. To further explore the nature and extent of the crosstalk between signaling and CME in cancer cell biology, we analyzed a panel of oncogenic signaling kinase inhibitors for their effects on CME across a panel of normal and cancerous cells. Inhibition of several kinases selectively affected CME in cancer cells, including inhibition of ERK1/2, which selectively inhibited CME by decreasing the rate of clathrin-coated pit (CCP) initiation. We identified an ERK1/2 substrate, the FCH/F-BAR and SH3 domain-containing protein FCHSD2, as being essential for the ERK1/2-dependent effects on CME and CCP initiation. Our data suggest that ERK1/2 phosphorylation activates FCHSD2 and regulates EGF receptor (EGFR) endocytic trafficking as well as downstream signaling activities. Loss of FCHSD2 activity in nonsmall cell lung cancer (NSCLC) cells leads to increased cell-surface expression and altered signaling downstream of EGFR, resulting in enhanced cell proliferation and migration. The expression level of FCHSD2 is positively correlated with higher NSCLC patient survival rates, suggesting that FCHSD2 can negatively affect cancer progression. These findings provide insight into the mechanisms and consequences of the reciprocal regulation of signaling and CME in cancer cells.

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Analysis for Carom complex signaling and function by database mining

Cited by 6 publications

References 45 publications

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

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

Cardiovascular Disease Risk Factors, Immune Checkpoints and Tregs

Role for ERK1/2-dependent activation of FCHSD2 in cancer cell-selective regulation of clathrin-mediated endocytosis

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