Cytoplasmic targeting signals mediate delivery of phospholemman to the plasma membrane

Lansbery, Kristan L.; Burcea, Lauren C.; Mendenhall, Margaretta L.; Mercer, Robert W.

doi:10.1152/ajpcell.00110.2005

Cited by 25 publications

(35 citation statements)

References 59 publications

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“…1A). Because phosphorylation at a specific residue of FXYD1 (PLM) was found to result in transportation of PLM from an intracellular compartment to the plasma membrane (Lansbery et al, 2006), phosphorylation may also play an important role in transport of pFXYD in gill epithelial cells of pufferfish. The intracellular transport mechanisms of pFXYD protein should be investigated in future studies.…”

Section: Discussionmentioning

confidence: 99%

Branchial FXYD protein expression in response to salinity change and its interaction with Na+/K+-ATPase of the euryhaline teleost Tetraodon nigroviridis

Wang

Lin

Hwang

et al. 2008

Journal of Experimental Biology

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Section: Discussionmentioning

confidence: 99%

Branchial FXYD protein expression in response to salinity change and its interaction with Na+/K+-ATPase of the euryhaline teleost Tetraodon nigroviridis

Wang

Lin

Hwang

et al. 2008

Journal of Experimental Biology

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“…Palmer et al (22) sequenced the FXYD1 protein by standard Edman degradation techniques, and several possible phosphorylation sites in the COOH terminus end (in one-letter notation: T 59 FRSSIRRLSTRRR 72 ) were suggested. On the basis of previous results (8,14,22,34), three possible phosphorylation sites on the human FXYD1 protein were selected for further investigation, namely at ser63, ser68, and thr69. Motif and phosphospecific antibodies targeted against each of the possible sites were commercially obtained (no.…”

Section: Methodsmentioning

confidence: 99%

Protein kinase Cα activity is important for contraction-induced FXYD1 phosphorylation in skeletal muscle

Thomassen

Rose

Jensen

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Thomassen M, Rose AJ, Jensen TE, Maarbjerg SJ, Bune L, Leitges M, Richter EA, Bangsbo J, Nordsborg NB. Protein kinase C␣ activity is important for contraction-induced FXYD1 phosphorylation in skeletal muscle. Am J Physiol Regul Integr Comp Physiol 301: R1808 -R1814, 2011. First published September 28, 2011 doi:10.1152/ajpregu.00066.2011.-Exercise-induced phosphorylation of FXYD1 is a potential important regulator of Na ϩ -K ϩ -pump activity. It was investigated whether skeletal muscle contractions induce phosphorylation of FXYD1 and whether protein kinase C␣ (PKC␣) activity is a prerequisite for this possible mechanism. In part 1, human muscle biopsies were obtained at rest, after 30 s of high-intensity exercise (166 Ϯ 31% of V O2max) and after a subsequent 20 min of moderate-intensity exercise (79 Ϯ 8% of V O2max). In general, FXYD1 phosphorylation was increased compared with rest both after 30 s (P Ͻ 0.05) and 20 min (P Ͻ 0.001), and more so after 20 min compared with 30 s (P Ͻ 0.05). Specifically, FXYD1 ser63, ser68, and combined ser68 and thr69 phosphorylation were 26 -45% higher (P Ͻ 0.05) after 20 min of exercise than at rest. In part 2, FXYD1 phosphorylation was investigated in electrically stimulated soleus and EDL muscles from PKC␣ knockout (KO) and wild-type (WT) mice. Contractile activity caused FXYD1 ser68 phosphorylation to be increased (P Ͻ 0.001) in WT soleus muscles but to be reduced (P Ͻ 0.001) in WT extensor digitorum longus. In contrast, contractile activity did not affect FXYD1 ser68 phosphorylation in the KO mice. In conclusion, exercise induces FXYD1 phosphorylation at multiple sites in human skeletal muscle. In mouse muscles, contraction-induced changes in FXYD1 ser68 phosphorylation are fiber-type specific and dependent on PKC␣ activity.

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“…NMR (10) and infrared spectroscopy (2) showed that the TM domain of PLM reconstituted in liposomes is an ␣-helix with a maximum tilt of 15-17°. Specifically, NMR spectroscopic studies of highly purified PLM in model micelles indicate that the molecule consists of four ␣-helices: H1 (residues [12][13][14][15][16][17] is in the extracellular NH 2 terminus, H2 (residues [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] is the main TM helix followed by the short H3 (residues 39 -45), and H4 (residues 60 -68) in the COOH terminus is connected to H3 by a flexible linker (36). PKA phosphorylates Ser 68 , whereas PKC phosphorylates Ser 63 and Ser 68 , of PLM (37).…”

mentioning

confidence: 99%

“…In addition, PLM is also a substrate for myotonic dystrophy protein kinase (23) and never in mitosis A kinase (19). In transfected Madin-Darby canine kidney cells expressing mouse PLM, phosphorylation of Ser 69 is important in shifting the distribution of PLM from the endoplasmic reticulum to the plasma membrane (16).…”

mentioning

confidence: 99%

Phospholemman regulates cardiac Na⁺/Ca²⁺ exchanger by interacting with the exchanger's proximal linker domain

Zhang

Wang²,

Carl³

et al. 2009

American Journal of Physiology-Cell Physiology

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Phospholemman (PLM) belongs to the FXYD family of small ion transport regulators. When phosphorylated at Ser 68 , PLM inhibits cardiac Na ϩ /Ca 2ϩ exchanger (NCX1). We previously demonstrated that the cytoplasmic tail of PLM interacts with the proximal intracellular loop (residues 218 -358), but not the transmembrane (residues 1-217 and 765-938) or Ca 2ϩ -binding (residues 371-508) domains, of NCX1. In this study, we used intact Na ϩ /Ca 2ϩ exchanger with various deletions in the intracellular loop to map the interaction sites with PLM. We first demonstrated by Western blotting and confocal immunofluorescence microscopy that wild-type (WT) NCX1 and its deletion mutants were expressed in transfected HEK-293 cells. Cotransfection with PLM and NCX1 (or its deletion mutants) in HEK-293 cells did not decrease expression of NCX1 (or its deletion mutants). Coexpression of PLM with WT NCX1 inhibited NCX1 current (INaCa). Deletion of residues 240 -679, 265-373, 250 -300, or 300 -373 from WT NCX1 resulted in loss of inhibition of INaCa by PLM. Inhibition of INaCa by PLM was preserved when residues 229 -237, 270 -300, 328 -330, or 330 -373 were deleted from the intracellular loop of NCX1. These results suggest that PLM mediated inhibition of INaCa by interacting with two distinct regions (residues 238 -270 and 300 -328) of NCX1. Indeed, INaCa measured in mutants lacking residues 238 -270, 300 -328, or 238 -270 ϩ 300 -328 was not affected by PLM. Glutathione S-transferase pull-down assays confirmed that PLM bound to fragments corresponding to residues 218 -371, 218 -320, 218 -270, 238 -371, and 300 -373, but not to fragments encompassing residues 250 -300 and 371-508 of NCX1, indicating that residues 218 -270 and 300 -373 physically associated with PLM. Finally, acute regulation of INaCa by PLM phosphorylation observed with WT NCX1 was absent in 250 -300 deletion mutant but preserved in 229 -237 deletion mutant. We conclude that PLM mediates its inhibition of NCX1 by interacting with residues 238 -270 and 300 -328. FXYD1; ion transport; sodium-calcium exchange PHOSPHOLEMMAN (PLM), the first cloned member of the FXYD family of regulators of ion transport (35), is a 72-amino acid sarcolemmal protein with a single transmembrane (TM) domain (27). The signature PFXYD motif is located in the extracellular NH 2 terminus. The cytoplasmic tail of human, rat, and dog PLM contains three serines (at residues 62, 63, and 68) and one threonine (at residue 69), but Thr 69 is replaced by serine in mouse PLM. NMR (10) and infrared spectroscopy (2) showed that the TM domain of PLM reconstituted in liposomes is an ␣-helix with a maximum tilt of 15-17°. Specifically, NMR spectroscopic studies of highly purified PLM in model micelles indicate that the molecule consists of four ␣-helices: H1 (residues 12-17) is in the extracellular NH 2 terminus, H2 (residues 22-38) is the main TM helix followed by the short H3 (residues 39 -45), and H4 (residues 60 -68) in the COOH terminus is connected to H3 by a flexible linker (36

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Cytoplasmic targeting signals mediate delivery of phospholemman to the plasma membrane

Abstract: Lansbery, Kristan L., Lauren C. Burcea, Margaretta L. Mendenhall, and Robert W. Mercer. Cytoplasmic targeting signals mediate delivery of phospholemman to the plasma membrane.

Cited by 25 publications

References 59 publications

Branchial FXYD protein expression in response to salinity change and its interaction with Na+/K+-ATPase of the euryhaline teleost Tetraodon nigroviridis

Branchial FXYD protein expression in response to salinity change and its interaction with Na+/K+-ATPase of the euryhaline teleost Tetraodon nigroviridis

Protein kinase Cα activity is important for contraction-induced FXYD1 phosphorylation in skeletal muscle

Phospholemman regulates cardiac Na⁺/Ca²⁺ exchanger by interacting with the exchanger's proximal linker domain

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Cytoplasmic targeting signals mediate delivery of phospholemman to the plasma membrane

Abstract: Lansbery, Kristan L., Lauren C. Burcea, Margaretta L. Mendenhall, and Robert W. Mercer. Cytoplasmic targeting signals mediate delivery of phospholemman to the plasma membrane.

Cited by 25 publications

References 59 publications

Branchial FXYD protein expression in response to salinity change and its interaction with Na+/K+-ATPase of the euryhaline teleost Tetraodon nigroviridis

Branchial FXYD protein expression in response to salinity change and its interaction with Na+/K+-ATPase of the euryhaline teleost Tetraodon nigroviridis

Protein kinase Cα activity is important for contraction-induced FXYD1 phosphorylation in skeletal muscle

Phospholemman regulates cardiac Na+/Ca2+ exchanger by interacting with the exchanger's proximal linker domain

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Phospholemman regulates cardiac Na⁺/Ca²⁺ exchanger by interacting with the exchanger's proximal linker domain