PI3K class II α regulates δ-opioid receptor export from the<i>trans</i>-Golgi network

Shiwarski, Daniel J.; Darr, Marlena; Telmer, Cheryl A.; Bruchez, Marcel P.; Puthenveedu, Manojkumar A.

doi:10.1091/mbc.e17-01-0030

Cited by 44 publications

(56 citation statements)

References 89 publications

(129 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although this FAP reporter was first developed in yeast (23), surprisingly it has not been used to detect the residence of membrane proteins at the cell surface in this organism. Instead, it has been applied only to monitor protein trafficking in mammalian cells (24,25). As hypothesized, we were able to demonstrate that Ldb19, Aly1, and Aly2 increase the cell-surface pool of Kir2.1, which they do by increasing Kir2.1 delivery to the plasma membrane rather than by reducing Kir2.1 endocytic turnover.…”

Section: Lating An Additional Class Of Plasma Membrane Proteins and Esupporting

confidence: 51%

Select α-arrestins control cell-surface abundance of the mammalian Kir2.1 potassium channel in a yeast model

Hager

Krasowski

Mackie

et al. 2018

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Protein composition at the plasma membrane is tightly regulated, with rapid protein internalization and selective targeting to the cell surface occurring in response to environmental changes. For example, ion channels are dynamically relocalized to or from the plasma membrane in response to physiological alterations, allowing cells and organisms to maintain osmotic and salt homeostasis. To identify additional factors that regulate the selective trafficking of a specific ion channel, we used a yeast model for a mammalian potassium channel, the K inward rectifying channel Kir2.1. Kir2.1 maintains potassium homeostasis in heart muscle cells, and Kir2.1 defects lead to human disease. By examining the ability of Kir2.1 to rescue the growth of yeast cells lacking endogenous potassium channels, we discovered that specific α-arrestins regulate Kir2.1 localization. Specifically, we found that the Ldb19/Art1, Aly1/Art6, and Aly2/Art3 α-arrestin adaptor proteins promote Kir2.1 trafficking to the cell surface, increase Kir2.1 activity at the plasma membrane, and raise intracellular potassium levels. To better quantify the intracellular and cell-surface populations of Kir2.1, we created fluorogen-activating protein fusions and for the first time used this technique to measure the cell-surface residency of a plasma membrane protein in yeast. Our experiments revealed that two α-arrestin effectors also control Kir2.1 localization. In particular, both the Rsp5 ubiquitin ligase and the protein phosphatase calcineurin facilitated the α-arrestin-mediated trafficking of Kir2.1. Together, our findings implicate α-arrestins in regulating an additional class of plasma membrane proteins and establish a new tool for dissecting the trafficking itinerary of any membrane protein in yeast.

show abstract

Section: Lating An Additional Class Of Plasma Membrane Proteins and Esupporting

confidence: 51%

Select α-arrestins control cell-surface abundance of the mammalian Kir2.1 potassium channel in a yeast model

Hager

Krasowski

Mackie

et al. 2018

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…GPCR organization in the plasma membrane is driven through receptor‐receptor, receptor‐lipid and receptor‐protein interactions that restrict and regulate receptor movement within the plasma membrane (Figure ). Most GPCRs begin their signaling lives at the plasma membrane, although some receptors are basally localized to intracellular sites such as the ER or the trans Golgi network . Once delivered to the plasma membrane, the three types of receptor interactions described below help GPCRs localize to specialized membrane domains and to specialized structures such as the neuronal postsynaptic density, primary cilia, and the outer segment of photoreceptor cells …”

Section: Basal Receptor Localization and Agonist‐dependent Redistribumentioning

confidence: 99%

Regulation of G protein‐coupled receptor signaling by plasma membrane organization and endocytosis

Weinberg

Puthenveedu

2019

Traffic

Self Cite

View full text Add to dashboard Cite

The trafficking of G protein coupled‐receptors (GPCRs) is one of the most exciting areas in cell biology because of recent advances demonstrating that GPCR signaling is spatially encoded. GPCRs, acting in a diverse array of physiological systems, can have differential signaling consequences depending on their subcellular localization. At the plasma membrane, GPCR organization could fine‐tune the initial stages of receptor signaling by determining the magnitude of signaling and the type of effectors to which receptors can couple. This organization is mediated by the lipid composition of the plasma membrane, receptor‐receptor interactions, and receptor interactions with intracellular scaffolding proteins. GPCR organization is subsequently changed by ligand binding and the regulated endocytosis of these receptors. Activated GPCRs can modulate the dynamics of their own endocytosis through changing clathrin‐coated pit dynamics, and through the scaffolding adaptor protein β‐arrestin. This endocytic regulation has signaling consequences, predominantly through modulation of the MAPK cascade. This review explores what is known about receptor sorting at the plasma membrane, protein partners that control receptor endocytosis, and the ways in which receptor sorting at the plasma membrane regulates downstream trafficking and signaling.

show abstract

“…The class I PI3Ks (PI3Ka, PI3Kb, PI3Kg, and PI3Kd) are heterodimers that predominantly recognize PtdIns 4,5-bisphosphate (PtdIns(4,5)P 2 ) to produce PtdIns (3,4,5)-trisphosphate (PtdIns(3,4,5)P 3 ) at the plasma membrane; for example, after antigen receptor activation (Hawkins et al, 2006;Vanhaesebroeck et al, 2010). Class II (PI3K-C2a, PI3K-C2b, and PI3K-C2g) and class III PI3Ks are known to produce PtdIns3P in distinct cellular compartments (Domin et al, 2000;Franco et al, 2014;Petiot et al, 2000;Shiwarski et al, 2017). VPS34, the sole class III PI3K, is a key regulator of autophagosome formation through the synthesis of PtdIns3P (Backer, 2016;Herman and Emr, 1990;Petiot et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Molecular Basis for Membrane Recruitment by the PX and C2 Domains of Class II Phosphoinositide 3-Kinase-C2α

et al. 2018

View full text Add to dashboard Cite

Phosphorylation of phosphoinositides by the class II phosphatidylinositol 3-kinase (PI3K) PI3K-C2a is essential for many processes, including neuroexocytosis and formation of clathrin-coated vesicles. A defining feature of the class II PI3Ks is a C-terminal module composed of phox-homology (PX) and C2 membrane interacting domains; however, the mechanisms that control their specific cellular localization remain poorly understood. Here we report the crystal structure of the C2 domain of PI3K-C2a in complex with the phosphoinositide head-group mimic inositol hexaphosphate, revealing two distinct pockets for membrane binding. The C2 domain preferentially binds to phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol (3,4,5)trisphosphate, and low-resolution structures of the combined PX-C2 module by small-angle X-ray scattering reveal a compact conformation in which cooperative lipid binding by each domain binding can occur. Finally, we demonstrate an unexpected role for calcium in perturbing the membrane interactions of the PX-C2 module, which we speculate may be important for regulating the activity of PI3K-C2a.

show abstract

PI3K class II α regulates δ-opioid receptor export from thetrans-Golgi network

Cited by 44 publications

References 89 publications

Select α-arrestins control cell-surface abundance of the mammalian Kir2.1 potassium channel in a yeast model

Select α-arrestins control cell-surface abundance of the mammalian Kir2.1 potassium channel in a yeast model

Regulation of G protein‐coupled receptor signaling by plasma membrane organization and endocytosis

Molecular Basis for Membrane Recruitment by the PX and C2 Domains of Class II Phosphoinositide 3-Kinase-C2α

Contact Info

Product

Resources

About