Signaling-mediated control of ubiquitin ligases in endocytosis. BMC Biol 10:25

IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139, Milan, Italy.
BMC Biology (Impact Factor: 7.98). 03/2012; 10(1):25. DOI: 10.1186/1741-7007-10-25
Source: PubMed


Ubiquitin-dependent regulation of endocytosis plays an important part in the control of signal transduction, and a critical issue in the understanding of signal transduction therefore relates to regulation of ubiquitination in the endocytic pathway. We discuss here what is known of the mechanisms by which signaling controls the activity of the ubiquitin ligases that specifically recognize the targets of ubiquitination on the endocytic pathway, and suggest alternative mechanisms that deserve experimental investigation.

    • "Mono-ubiquitinylation of one or more lysine residues is generally associated with endocytosis of membrane proteins (Polo, 2012), but polyubiquitinylation (attachment of multiple ubiquitin molecules linked together in a linear or branched fashion) generally marks proteins for proteasomal or vacuolar degradation. For example, polyubiquitinylation of the brassinosteroid receptor BRI1 marks it for endocytosis and targeting to the vacuole (Martins et al. 2015). "
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    ABSTRACT: The tomato Cf-9 gene encodes a membrane-anchored glycoprotein that imparts race-specific resistance against the tomato leaf mould fungus Cladosporium fulvum in response to the avirulence protein Avr9. While the N-terminal half of the extracellular leucine-rich repeat (eLRR) domain of Cf-9 protein determines its specificity for Avr9, the C-terminal half including its small cytosolic domain is postulated to be involved in signalling. The cytosolic domain of Cf-9 carries several residues that are potential sites for ubiquitinylation or phosphorylation, or signals for endocytic uptake. A targeted mutagenesis approach was employed to investigate the roles of these residues and cellular processes in Avr9-dependent necrosis triggered by Cf-9. Our results indicate that the membrane-proximal region of the cytosolic domain of Cf-9 plays an important role in Cf-9-mediated necrosis and two amino acids within this region, a threonine (T835) and a proline (P838) are particularly important for Cf-9 function. An alanine mutation of T835 had no effect on Cf-9 function but an aspartic acid mutation, which mimics phosphorylation, reduced Cf-9 function. We therefore postulate that phosphorylation/de-phosphorylation of T835 could act as a molecular switch to determine whether Cf-9 is in a primed or inactive state. Yeast-two-hybrid analysis was used to show that the cytosolic domain of Cf-9 interacts with the cytosolic domain of tomato VAP27. This interaction could be disrupted by an alanine mutation of P838, whereas interaction with CITRX remained unaffected. We therefore postulate that a proline-induced kink in the membrane-proximal region of the cytosolic domain of Cf-9 may be important for interaction with VAP27, which may in turn be important for Cf-9 function. This article is protected by copyright. All rights reserved.
    No preview · Article · Aug 2015 · Molecular Plant Pathology
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    • "However, in pollen tubes, very little is known about the mechanisms of either selective internalization or molecular sorting. Posttranslational modifications such as phosphorylation, ubiquitylation, and sumoylation (the covalent binding of small ubiquitin-related modifier proteins (SUMO)) trigger endocytosis of membrane proteins, which is important for the sorting of internalized proteins in early endosomes (Slepnev et al., 1998; Umebayashi, 2003; Urbe, 2005; Martin et al., 2007; Polo, 2012; Urano et al., 2012). "
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    ABSTRACT: Pollen tubes elongate rapidly at their tips through highly polarized cell growth known as tip growth. Tip growth requires intensive exocytosis at the tip, which is supported by a dynamic cytoskeleton and vesicle trafficking. Several signaling pathways have been demonstrated to coordinate pollen tube growth by regulating cellular activities such as actin dynamics, exocytosis, and endocytosis. These signaling pathways crosstalk to form a signaling network that coordinates the cellular processes required for tip growth. The homeostasis of key signaling molecules is critical for the proper elongation of the pollen tube tip, and is commonly fine-tuned by positive and negative regulations. In addition to the major signaling pathways, emerging evidence implies the roles of other signals in the regulation of pollen tube growth. Here we review and discuss how these signaling networks modulate the rapid growth of pollen tubes.
    Full-text · Article · Jul 2013 · Molecular Plant
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    • "Also, the study of the amiloride-sensitive epithelial sodium channel ENaC clearly established that its ubiquitylation regulates the channel's stability [58]. Subsequent work on ENaC, GHR, and many other receptors (such as EGFR, PDGFR, c-Met, TGF-βR, β2-AR) confirmed the critical function of ubiquitin in endocytosis in mammals [23] [59] [60]. However, where this ubiquitylation occurs in the cell (plasma membrane or endosomal compartments), and how ubiquitylation impacts on the target receptor's fate (internalization, progression through the endocytic pathway, or degradation) are still a matter of debate and seem to vary upon the receptor and the physiological situation considered [61]. "
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    ABSTRACT: In metazoans, proteins of the arrestin family are key players of G-protein-coupled receptors (GPCRS) signaling and trafficking. Following stimulation, activated receptors are phosphorylated, thus allowing the binding of arrestins and hence an "arrest" of receptor signaling. Arrestins act by uncoupling receptors from G proteins and contribute to the recruitment of endocytic proteins, such as clathrin, to direct receptor trafficking into the endocytic pathway. Arrestins also serve as adaptor proteins by promoting the recruitment of ubiquitin ligases and participate in the agonist-induced ubiquitylation of receptors, known to have impact on their subcellular localization and stability. Recently, the arrestin family has expanded following the discovery of arrestin-related proteins in other eukaryotes such as yeasts or fungi. Surprisingly, most of these proteins are also involved in the ubiquitylation and endocytosis of plasma membrane proteins, thus suggesting that the role of arrestins as ubiquitin ligase adaptors is at the core of these proteins' functions. Importantly, arrestins are themselves ubiquitylated, and this modification is crucial for their function. In this paper, we discuss recent data on the intricate connections between arrestins and the ubiquitin pathway in the control of endocytosis.
    Full-text · Article · Sep 2012
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