Antagonistic regulation controls clathrin-mediated endocytosis: AP2 adaptor facilitation vs restraint from clathrin light chains

Redlingshöfer, Lisa; Brodsky, Frances M.

doi:10.1016/j.cdev.2021.203714

Cited by 10 publications

(7 citation statements)

References 102 publications

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“…The AP2 complex recognizes conserved motifs in the cytoplasmic domain of target proteins through the AP2μ2 subunit ( Chen et al, 2011 ; Fan et al, 2015 ). In addition, the AP2 complex recruits clathrin components, fulfilling a critical dual function during CME ( Redlingshöfer and Brodsky, 2021 ). Therefore, we evaluated AP2 subcellular distribution in both growth conditions (with and without sucrose) using the AP2μ2-YFP reporter line ( Bashline et al, 2013 ).…”

Section: Resultsmentioning

confidence: 99%

“…The fact that AP2 vesicles are affected suggests that sucrose-modulated CME drives protein internalization; however, the specificity of this process and the identity of cargo proteins remain unclear. Recruitment of AP2 at the endocytic pit requires PI(4,5)P 2 -enriched plasma membrane domains, which may be important in the regulation of CME ( Redlingshöfer and Brodsky, 2021 ). Our results show a lower abundance of PI(4,5)P 2 associated with a higher rate of vesicle internalization ( Figures 3 , 5 ) in the presence of sucrose, suggesting that the metabolism of phosphoinositides is a primary target for CME modulation by this sugar.…”

Section: Sucrose As a Regulator Of Endocytic Traffickingmentioning

confidence: 99%

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Sucrose targets clathrin-mediated endocytosis kinetics supporting cell elongation in Arabidopsis thaliana

2022

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Sucrose is a central regulator of plant growth and development, coordinating cell division and cell elongation according to the energy status of plants. Sucrose is known to stimulate bulk endocytosis in cultured cells; however, its physiological role has not been described to date. Our work shows that sucrose supplementation induces root cell elongation and endocytosis. Sucrose targets clathrin-mediated endocytosis (CME) in epidermal cells. Its presence decreases the abundance of both the clathrin coating complex and phosphatidylinositol 4,5-biphosphate at the plasma membrane, while increasing clathrin complex abundance in intracellular spaces. Sucrose decreases the plasma membrane residence time of the clathrin complex, indicating that it controls the kinetics of endocytic vesicle formation and internalization. CME regulation by sucrose is inducible and reversible; this on/off mechanism reveals an endocytosis-mediated mechanism for sensing plant energy status and signaling root elongation. The sucrose monosaccharide fructose also induces CME, while glucose and mannitol have no effect, demonstrating the specificity of the process. Overall, our data show that sucrose can mediate CME, which demonstrates that sucrose signaling for plant growth and development is dependent on endomembrane trafficking.

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Section: Resultsmentioning

confidence: 99%

Section: Sucrose As a Regulator Of Endocytic Traffickingmentioning

confidence: 99%

Sucrose targets clathrin-mediated endocytosis kinetics supporting cell elongation in Arabidopsis thaliana

2022

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“…Indeed, recent phylogenetic studies identifying CLCs of highly divergent sequences in protist eukaryotes (Santos et al, 2022) indicate that CLC equivalents are predicted to interact with the TxD of CHC17 equivalents, and that this may be the essential molecular requirement for a CHC-associated subunit. As SNX5/6 interacts principally with the TxD of CHC22 rather spanning the proximal leg of the heavy chain to the knee where CLC affects CHC17 assembly dynamics (Redlingshöfer and Brodsky, 2021), one possibility is that SNX5/6 binding influences the CHC22 uncoating dynamics. CHC22 has markedly different uncoating properties to CHC17 (Dannhauser et al, 2017) and the truncation of the TxD in CHC22 relative to CHC17, losing the recognition site for the uncoating ATPase (Rapoport et al, 2008), is the most striking distinction between the two clathrin isoforms (Liu et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

CHC22 clathrin functions in the early secretory pathway by two-site interaction with SNX5 and p115

Greig

Bates

Yin

et al. 2022

Preprint

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The two clathrin isoforms, CHC17 and CHC22, generate separate vesicles for intracellular transport. CHC17 mediates endocytosis and housekeeping membrane traffic in all cells. CHC22, expressed most highly in skeletal muscle, transports the glucose transporter GLUT4 from the endoplasmic-reticulum-to-Golgi intermediate compartment (ERGIC) to an intracellular GLUT4 storage compartment (GSC) from where GLUT4 is mobilized by insulin. Molecular determinants distinguishing the trafficking of CHC22 clathrin from CHC17 within the GLUT4 pathway are defined in this study. The C-terminal trimerization domain of CHC22, but not CHC17, directly binds SNX5, which also binds the ERGIC tether p115. SNX5, and the functionally redundant SNX6, are required for CHC22 localization independently of their participation in the endosomal ESCPE-1 complex. Both the SNX5-BAR domain and an isoform-specific patch on the CHC22 N-terminal domain separately mediate binding to p115, and both interactions are required for CHC22 recruitment. These indirect and direct interactions at each CHC22 terminus are required for GLUT4 traffic to the GSC, defining a dual mechanism regulating the function of CHC22 in glucose metabolism.Summary statementCHC22 clathrin uses a bipartite mechanism for recruitment to the early secretory pathway, where it targets the GLUT4 transporter to an insulin-responsive intracellular compartment. Localization requires binding to the ERGIC tether p115 through sorting nexin 5 interaction at the CHC22 C-terminus and directly via the CHC22 N-terminal domain.

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“…Eukaryotic cells take up molecules, such as extracellular proteins and lipoproteins, by a process called endocytosis, which includes clathrin-dependent or -independent endocytosis and micropinocytosis ( Figure 2 ) [ 259 , 260 , 261 , 262 , 263 , 264 , 265 , 266 , 267 , 268 , 269 ]. In clathrin-dependent endocytosis, when a ligand molecule binds to a receptor on the plasma membrane, a clathrin molecule binds to the cytosol via an AP2 adaptor protein, and a ball-shaped structure of the plasma membrane is formed [ 270 , 271 , 272 , 273 ].…”

Section: Ev Uptake In Target Cells Via Macropinocytosismentioning

confidence: 99%

Molecular Docking and Intracellular Translocation of Extracellular Vesicles for Efficient Drug Delivery

Matsuzaka

Yashiro

2022

IJMS

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Extracellular vesicles (EVs), including exosomes, mediate intercellular communication by delivering their contents, such as nucleic acids, proteins, and lipids, to distant target cells. EVs play a role in the progression of several diseases. In particular, programmed death-ligand 1 (PD-L1) levels in exosomes are associated with cancer progression. Furthermore, exosomes are being used for new drug-delivery systems by modifying their membrane peptides to promote their intracellular transduction via micropinocytosis. In this review, we aim to show that an efficient drug-delivery system and a useful therapeutic strategy can be established by controlling the molecular docking and intracellular translocation of exosomes. We summarise the mechanisms of molecular docking of exosomes, the biological effects of exosomes transmitted into target cells, and the current state of exosomes as drug delivery systems.

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Antagonistic regulation controls clathrin-mediated endocytosis: AP2 adaptor facilitation vs restraint from clathrin light chains

Cited by 10 publications

References 102 publications

Sucrose targets clathrin-mediated endocytosis kinetics supporting cell elongation in Arabidopsis thaliana

Sucrose targets clathrin-mediated endocytosis kinetics supporting cell elongation in Arabidopsis thaliana

CHC22 clathrin functions in the early secretory pathway by two-site interaction with SNX5 and p115

Molecular Docking and Intracellular Translocation of Extracellular Vesicles for Efficient Drug Delivery

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