Plasma membrane domains enriched in cortical endoplasmic reticulum function as membrane protein trafficking hubs

Fox, Philip D.; Haberkorn, Christopher J.; Weigel, Aubrey V.; Higgins, Jenny L.; Akin, Elizabeth J.; Kennedy, Matthew J.; Krapf, Diego; Tamkun, Michael M.

doi:10.1091/mbc.e12-12-0895

Cited by 34 publications

(40 citation statements)

References 57 publications

(38 reference statements)

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“…Early electron microscopy analyses of Kv2.1 immuno-gold labeling in the hippocampus have indicated that Kv2.1 clusters localize above SSCs that are juxtaposed to astrocytic processes (Du et al, 1998), and fluorescence microscopy analyses of live cultured cells shows that Kv2.1 clusters reside atop projections of the ER that terminate near the plasma membrane -i.e. cortical ER (cER) (Fox et al, 2013a). Consistent with these observations, Kv2.1 clusters on the soma and axon initial segment partially colocalize with ryanodine receptors (RyRs) in culture and in the intact brain (King et al, 2014;Lim et al, 2000;Mandikian et al, 2014).…”

Section: Introductionsupporting

confidence: 57%

“…The majority of experiments utilizing light microscopy were performed using TIRF microscopy to restrict illumination to within ∼100 nm of the basal surface of the cell in order to visualize the cER (Fox et al, 2013a). Transfected HEK cells and neurons were imaged with a Nikon Eclipse Ti Perfect-Focus equipped TIRF/widefield fluorescence microscope equipped with AOTF controlled 405, 488, 543 nm diode lasers, 100 mW each, and an Intensilight wide-field light source.…”

Section: Tirf Microscopymentioning

confidence: 99%

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Induction of stable ER–plasma-membrane junctions by Kv2.1 potassium channels

Fox

Haberkorn

Akin

et al. 2015

Journal of Cell Science

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106

158

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Section: Introductionsupporting

confidence: 57%

Section: Tirf Microscopymentioning

confidence: 99%

Induction of stable ER–plasma-membrane junctions by Kv2.1 potassium channels

Fox

Haberkorn

Akin

et al. 2015

Journal of Cell Science

Self Cite

106

158

View full text Add to dashboard Cite

show abstract

“…3D,F), suggesting that the decreased current density displayed by the LQT5 mutant does not seem to be accounted for by trafficking defects. However, TIRF does not allow discrimination between the signals from the plasma membrane and those arising from the cortical ER, which is especially relevant for some K + channels (Fox et al, 2013). Thus, an effect on trafficking cannot be totally excluded.…”

Section: C-terminusmentioning

confidence: 99%

Long QT mutations disrupt IKS regulation by PKA and PIP2 at the same KCNQ1 helix C-KCNE1 interface

Dvir

Strulovich

Sachyani

et al. 2014

Journal of Cell Science

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KCNQ1 and KCNE1 co-assembly generates the I KS K + current, which is crucial to the cardiac action potential repolarization. Mutations in their corresponding genes cause long QT syndrome (LQT) and atrial fibrillation. The A-kinase anchor protein, yotiao (also known as AKAP9), brings the I KS channel complex together with signaling proteins to achieve regulation upon b1-adrenergic stimulation. Recently, we have shown that KCNQ1 helix C interacts with the KCNE1 distal C-terminus. We postulated that this interface is crucial for I KS channel modulation. Here, we examined the yet unknown molecular mechanisms of LQT mutations located at this intracellular intersubunit interface. All LQT mutations disrupted the internal KCNQ1-KCNE1 intersubunit interaction. LQT mutants in KCNQ1 helix C led to a decreased current density and a depolarizing shift of channel activation, mainly arising from impaired phosphatidylinositol-4,5-bisphosphate (PIP 2 ) modulation. In the KCNE1 distal C-terminus, the LQT mutation P127T suppressed yotiao-dependent cAMP-mediated upregulation of the I KS current, which was caused by reduced KCNQ1 phosphorylation at S27. Thus, KCNQ1 helix C is important for channel modulation by PIP 2 , whereas the KCNE1 distal C-terminus appears essential for the regulation of I KS by yotiao-mediated PKA phosphorylation.

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“…In this model, the cytoskeleton and its associated proteins establish diffusion barriers, and the energy-dependent constant delivery and removal of membrane proteins and lipids at the plasma membrane creates lateral variations in component abundance (Gheber and Edidin, 1999; Turner et al, 2005; Lavi et al, 2007; Fan et al, 2010). Indeed, localized trafficking hubs in the plasma membrane have been shown to produce stable domains of distinct protein compositions (Deutsch et al, 2012; Fox et al, 2013). Whether the sphingolipid domains in the plasma membrane are local hubs for sphingolipid trafficking might be assessed by performing high-resolution SIMS in a depth profiling mode to produce three-dimensional images of the intracellular sphingolipid distribution (Yeager et al, 2016).…”

Section: Implications For Plasma Membrane Organization Hypothesesmentioning

confidence: 99%

Sphingolipid Organization in the Plasma Membrane and the Mechanisms That Influence It

Kraft

2017

Front. Cell Dev. Biol.

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Sphingolipids are structural components in the plasma membranes of eukaryotic cells. Their metabolism produces bioactive signaling molecules that modulate fundamental cellular processes. The segregation of sphingolipids into distinct membrane domains is likely essential for cellular function. This review presents the early studies of sphingolipid distribution in the plasma membranes of mammalian cells that shaped the most popular current model of plasma membrane organization. The results of traditional imaging studies of sphingolipid distribution in stimulated and resting cells are described. These data are compared with recent results obtained with advanced imaging techniques, including super-resolution fluorescence detection and high-resolution secondary ion mass spectrometry (SIMS). Emphasis is placed on the new insight into the sphingolipid organization within the plasma membrane that has resulted from the direct imaging of stable isotope-labeled lipids in actual cell membranes with high-resolution SIMS. Super-resolution fluorescence techniques have recently revealed the biophysical behaviors of sphingolipids and the unhindered diffusion of cholesterol analogs in the membranes of living cells are ultimately in contrast to the prevailing hypothetical model of plasma membrane organization. High-resolution SIMS studies also conflicted with the prevailing hypothesis, showing sphingolipids are concentrated in micrometer-scale membrane domains, but cholesterol is evenly distributed within the plasma membrane. Reductions in cellular cholesterol decreased the number of sphingolipid domains in the plasma membrane, whereas disruption of the cytoskeleton eliminated them. In addition, hemagglutinin, a transmembrane protein that is thought to be a putative raft marker, did not cluster within sphingolipid-enriched regions in the plasma membrane. Thus, sphingolipid distribution in the plasma membrane is dependent on the cytoskeleton, but not on favorable interactions with cholesterol or hemagglutinin. The alternate views of plasma membrane organization suggested by these findings are discussed.

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Plasma membrane domains enriched in cortical endoplasmic reticulum function as membrane protein trafficking hubs

Cited by 34 publications

References 57 publications

Induction of stable ER–plasma-membrane junctions by Kv2.1 potassium channels

Induction of stable ER–plasma-membrane junctions by Kv2.1 potassium channels

Long QT mutations disrupt IKS regulation by PKA and PIP2 at the same KCNQ1 helix C-KCNE1 interface

Sphingolipid Organization in the Plasma Membrane and the Mechanisms That Influence It

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