Endocytosis of G Protein-Coupled Receptors Is Regulated by Clathrin Light Chain Phosphorylation

Ferreira, Filipe; Foley, Michael; Cooke, Alex; Cunningham, Margaret; Smith, Gemma; Woolley, Robert; Henderson, Graeme; Kelly, Eamonn; Mundell, Stuart J; Smythe, Elizabeth

doi:10.1016/j.cub.2012.05.034

Cited by 42 publications

(55 citation statements)

References 37 publications

(66 reference statements)

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“…Such aggregation, mediated by ubiquitination or other pathways, is likely to change membrane-bending properties that could then require extra tensile strength provided by CLCs in the clathrin coat. Mutagenesis studies suggest that CLC phosphorylation by GRK2 may contribute to regulation of CLC's role in GPCR cargo selection (5). Whether CLC phosphorylation is also involved in uptake of the CLC-dependent receptors identified here is not yet established.…”

Section: Clc Depletion From Cell Lines Establishes Selectivity For DImentioning

confidence: 86%

“…Analogously, Sec13p in COPII-coated vesicles contributes structural rigidity that is required to bend membranes with asymmetric cargo, such as GPI-anchored receptors (36). Two GPCR cargoes (μ-opioid receptor and CXCR4) that require CLCs for endocytosis are modified by ubiquitin, which attracts specific endocytic adaptors to promote uptake by clathrin-coated pits (5,31,37). Such aggregation, mediated by ubiquitination or other pathways, is likely to change membrane-bending properties that could then require extra tensile strength provided by CLCs in the clathrin coat.…”

Section: Clc Depletion From Cell Lines Establishes Selectivity For DImentioning

confidence: 99%

“…Depletion of both isoforms from tissue culture cells by siRNA treatment showed that CLCs are not required for clathrin-mediated uptake of classic CCV cargoes, such as transferrin receptor (TfR), epidermal growth factor receptor, or low-density lipoprotein receptor (2)(3)(4). CLCs were, however, implicated in uptake of three G protein-coupled receptors (GPCRs) (5). CLCs are also required for uptake of large particles, including some viruses and bacteria (6,7).…”

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confidence: 99%

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Clathrin light chains’ role in selective endocytosis influences antibody isotype switching

Majeed

Evans

et al. 2016

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

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Clathrin, a cytosolic protein composed of heavy and light chain subunits, assembles into a vesicle coat, controlling receptor-mediated endocytosis. To establish clathrin light chain (CLC) function in vivo, we engineered mice lacking CLCa, the major CLC isoform in B lymphocytes, generating animals with CLC-deficient B cells. In CLCa-null mice, the germinal centers have fewer B cells, and they are enriched for IgA-producing cells. This enhanced switch to IgA production in the absence of CLCa was attributable to increased transforming growth factor β receptor 2 (TGFβR2) signaling resulting from defective endocytosis. Internalization of C-X-C chemokine receptor 4 (CXCR4), but not CXCR5, was affected in CLCa-null B cells, and CLC depletion from cell lines affected endocytosis of the δ-opioid receptor, but not the β2-adrenergic receptor, defining a role for CLCs in the uptake of a subset of signaling receptors. This instance of clathrin subunit deletion in vertebrates demonstrates that CLCs contribute to clathrin’s role in vivo by influencing cargo selectivity, a function previously assigned exclusively to adaptor molecules.

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Section: Clc Depletion From Cell Lines Establishes Selectivity For DImentioning

confidence: 86%

Section: Clc Depletion From Cell Lines Establishes Selectivity For DImentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Clathrin light chains’ role in selective endocytosis influences antibody isotype switching

Majeed

Evans

et al. 2016

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

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“…However, CLCs are required for uptake of some Gprotein-coupled receptors (Ferreira et al 2012). As negative regulators of clathrin assembly, CLC may be dispensable for uptake of membrane that remains flexible with certain cargo, but CLC contribution to triskelion rigidity may be required for uptake of less forgiving cargo.…”

Section: Clathrin Light Chains and Their Influence On Binding Partnersmentioning

confidence: 99%

Diversity of Clathrin Function: New Tricks for an Old Protein

Brodsky

2012

Annu. Rev. Cell Dev. Biol.

187

194

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Clathrin is considered the prototype vesicle coat protein whose self-assembly mediates sorting of membrane cargo and recruitment of lipid modifiers. Detailed knowledge of clathrin biochemistry, structure, and interacting proteins has accumulated since the first observation, almost 50 years ago, of its role in receptor-mediated endocytosis of yolk protein. This review summarizes that knowledge, and focuses on properties of the clathrin heavy and light chain subunits and interaction of the latter with Hip proteins, to address the diversity of clathrin function beyond conventional receptor-mediated endocytosis. The distinct functions of the two human clathrin isoforms (CHC17 and CHC22) are discussed, highlighting CHC22's specialized involvement in traffic of the GLUT4 glucose transporter and consequent role in human glucose metabolism. Analysis of clathrin light chain function and interaction with the actin-binding Hip proteins during bacterial infection defines a novel actin-organizing function for CHC17 clathrin. By considering these diverse clathrin functions, along with intracellular sorting roles and influences on mitosis, further relevance of clathrin function to human health and disease is established.

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“…Intriguingly these two purinergic receptors appear to sort into distinct membrane clathrin coated pits, an observation that has been reported for other GPCRs (15). The mechanisms underlying P2Y 12 receptor internalization are complex and, as with receptor desensitization, are mediated in part by GRKs and arrestin (14,16,17). The small GTP-binding protein ARF6 (ADP-ribosylation factor 6) also plays a role in the internalization of P2Y 12 receptors in human platelets (16).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 66%

Pathophysiological consequences of receptor mistraffic: Tales from the platelet P2Y 12 receptor

Cunningham

Aungraheeta

Mundell

2017

Molecular and Cellular Endocrinology

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Endocytosis of G Protein-Coupled Receptors Is Regulated by Clathrin Light Chain Phosphorylation

Abstract: Together, these results indicate that CLCb phosphorylation acts as a discriminator for the endocytosis of specific GPCRs.

Cited by 42 publications

References 37 publications

Clathrin light chains’ role in selective endocytosis influences antibody isotype switching

Clathrin light chains’ role in selective endocytosis influences antibody isotype switching

Diversity of Clathrin Function: New Tricks for an Old Protein

Pathophysiological consequences of receptor mistraffic: Tales from the platelet P2Y 12 receptor

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