Dokument

Summary:
We have studied some of the mechanisms responsible for controlling the density of Kir2.1 channels at the cell surface. In particular, we have explored the mechanisms underlying the of Kir2.1 channel into the endocytic pathway. We found that 1. The antibody uptake assay showed that about 20% of the antibodies labeled surface channels were internalized within 5 min of temperature shift; an apparent maximum was reached after 15 min. Kir2.1 undergoes constitutive internalization. 2. Co-expression of a dominant-negative mutant of dynamin K44A or AP180C enhanced the surface expression of Kir2.1 by 40% and 49% respectively. AP180C inhibited clathrin mediated internalization of Kir2.1 by 80% compared with COS-7 cells transfected with Kir2.1 and a control vector. Kir2.1 is internalized by clathrin-mediated endocytosis. 3. In both Xenopus oocytes and mammalian cells system, disruption of Y242 and Y341 motif significantly increased the amount of Kir2.1 at cell surface respectively. The mutants Y242A and Y341A also showed dramatic decrease in the rate of endocytosis as compared to wild-type Kir2.1 channels respectively. Two tyrosine based endocytic motifs 242YIPL245 and 341YSRF344 in the C-terminal domain of Kir2.1 are both involved in the endocytosis of Kir2.1. 4. Live cell imaging clearly showed that Kir2.1 channels strongly colocalized with early endosomal marker, Rab5 or late endosomal marker, Rab7 or recycling endosome marker, Rab11 or Lyso-Tracker Red. Kir2.1 is targeted to the endosome-lysosomal and endosomal- recycling pathway. 5. The two endocytosis signals studied here are in close vicinity as indicated by the tertiary structure of the cytosolic pore of Kir2.1 channels. Since mutation of both motifs had the similar effect as mutation of only one of these motifs. We hypothesize that both signals must be present for efficient constitutive endocyosis to occur.

Bibliographie / References

1. Zeng W-Z, Babich V, Ortega B, Quigley R, White SJ, Welling PA & Huang C-L. (2002). Evidence for endocytosis of ROMK potassium channel via clathrin-coated vesicles. American Journal of Physiology-Renal Physiology 283, F630-F639.
2. Mason AK. (2008). Molecular mechanisms of endocytic and post-endocytic trafficking regulating Kir2. x channels. ProQuest.
3. Shieh C-C, Coghlan M, Sullivan JP & Gopalakrishnan M. (2000). Potassium channels: molecular defects, diseases, and therapeutic opportunities. Pharmacological Reviews 52, 557-594.
4. Sunder‐Plassmann R, Lialios F, Madsen M, Koyasu S & Reinherz EL. (1997). Functional analysis of immunoreceptor tyrosinebased activation motif (ITAM)‐mediated signal transduction: the two YxxL segments within a single CD3ζITAM are functionally distinct. European journal of immunology 27, 2001-2009.
5. Abraham MR, JAHANGIR A, ALEKSEEV AE & TERZIC A. (1999). Channelopathies of inwardly rectifying potassium channels. The FASEB journal 13, 1901-1910.
6. Varkevisser R, Houtman MJ, Waasdorp M, Man JC, Heukers R, Takanari H, Tieland RG, en Henegouwen PMvB, Vos MA & van der Heyden MA. (2013). Inhibiting the clathrin-mediated endocytosis pathway rescues KIR2. 1 downregulation by pentamidine. Pflügers Archiv-European Journal of Physiology 465, 247-259.
7. Gao Z, Lau C-P, Wong T-M & Li G-R. (2004). Protein tyrosine kinase- dependent modulation of voltage-dependent potassium channels by genistein in rat cardiac ventricular myocytes. Cellular signalling 16, 333- 341.
8. Hu K, Huang CS, Jan YN & Jan LY. (2003). ATP-sensitive potassium channel traffic regulation by adenosine and protein kinase C. Neuron 38, 417-432.
9. Margeta-Mitrovic M. (2002). Assembly-dependent trafficking assays in the detection of receptor–receptor interactions. Methods 27, 311-317.
10. HU W, HOWARD M & Lukacs G. (2001). Multiple endocytic signals in the C- terminal tail of the cystic fibrosis transmembrane conductance regulator. Biochem J 354, 561-572.
11. Sierra A, Zhu Z, Sapay N, Sharotri V, Kline CF, Luczak ED, Subbotina E, Sivaprasadarao A, Snyder PM & Mohler PJ. (2013). Regulation of cardiac ATP-sensitive potassium channel surface expression by calcium/calmodulin-dependent protein kinase II. Journal of Biological Chemistry 288, 1568-1581.
12. Vaidyanathan R, Vega AL, Song C, Zhou Q, Tan B, Berger S, Makielski JC & Eckhardt LL. (2013). The Interaction of Caveolin 3 Protein with the Potassium Inward Rectifier Channel Kir2. 1 PHYSIOLOGY AND PATHOLOGY RELATED TO LONG QT SYNDROME 9 (LQT9). Journal of Biological Chemistry 288, 17472-17480.
13. Kinlough CL, Poland PA, Bruns JB, Harkleroad KL & Hughey RP. (2004). MUC1 membrane trafficking is modulated by multiple interactions. Journal of Biological Chemistry 279, 53071-53077.
14. Pandey MS, Harris EN, Weigel JA & Weigel PH. (2008). The cytoplasmic domain of the hyaluronan receptor for endocytosis (HARE) contains multiple endocytic motifs targeting coated pit-mediated internalization. Journal of Biological Chemistry 283, 21453-21461.
15. Xu X, Kanda VA, Choi E, Panaghie G, Roepke TK, Gaeta SA, Christini DJ, Lerner DJ & Abbott GW. (2009). MinK-dependent internalization of the IKs potassium channel. Cardiovascular research.
16. De Boer T, Houtman M, Compier M & Van der Heyden M. (2010). The mammalian KIR2. x inward rectifier ion channel family: expression pattern and pathophysiology. Acta Physiologica 199, 243-256.
17. Jones SP. (2003). Role of the small GTPase Rho in modulation of the inwardly rectifying potassium channel Kir2. 1. Molecular Pharmacology 64, 987- 993.
18. Sun Y, Chen M, Lowentritt BH, Van Zijl PS, Koch KR, Keay S, Simard JM & Chai TC. (2007). EGF and HB-EGF modulate inward potassium current in human bladder urothelial cells from normal and interstitial cystitis patients. American Journal of Physiology-Cell Physiology 292, C106- C114.
19. Lu J-C, Scott P, Strous GJ & Schuler LA. (2002). Multiple internalization motifs differentially used by prolactin receptor isoforms mediate similar endocytic pathways. Molecular Endocrinology 16, 2515-2527.
20. Hinard V, Belin D, Konig S, Bader CR & Bernheim L. (2008). Initiation of human myoblast differentiation via dephosphorylation of Kir2. 1 K+ channels at tyrosine 242. Development 135, 859-867.
21. Liang S, Wang Q, Zhang W, Zhang H, Tan S, Ahmed A & Gu Y. (2014). Carbon monoxide inhibits inward rectifier potassium channels in cardiomyocytes. Nature communications 5.
22. Giovannardi S, Forlani G, Balestrini M, Bossi E, Tonini R, Sturani E, Peres A & Zippel R. (2002). Modulation of the inward rectifier potassium channel IRK1 by the Ras signaling pathway. Journal of Biological Chemistry 277, 12158-12163.
23. Hofherr A, Fakler B & Klöcker N. (2005). Selective Golgi export of Kir2. 1 controls the stoichiometry of functional Kir2. x channel heteromers. Journal of cell science 118, 1935-1943.
24. Scherer D, Kiesecker C, Kulzer M, Günth M, Scholz EP, Kathöfer S, Thomas D, Maurer M, Kreuzer J & Bauer A. (2007). Activation of inwardly rectifying Kir2. x potassium channels by β3-adrenoceptors is mediated via different signaling pathways with a predominant role of PKC for Kir2. 1 and of PKA for Kir2. 2. Naunyn-Schmiedeberg's archives of pharmacology 375, 311-322.
25. Golgi export of the Kir2. 1 channel is driven by a trafficking signal located within its tertiary structure. Cell 145, 1102-1115.
26. Bonifacino JS & Traub LM. (2003). Signals for Sorting of Transmembrane Proteins to Endosomes and Lysosomes*. Annual review of biochemistry 72, 395-447.
27. Grant B & Sato M. (2006). Intracellular trafficking (January 21, 2006), WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook. 1.77. 1.
28. Hibino H, Inanobe A, Furutani K, Murakami S, Findlay I & Kurachi Y. (2010). Inwardly rectifying potassium channels: their structure, function, and physiological roles. Physiological reviews 90, 291-366.
29. Seebohm G, Strutz-Seebohm N, Ursu ON, Preisig-Müller R, Zuzarte M, Hill EV, Kienitz M-C, Bendahhou S, Fauler M & Tapken D. (2012). Altered stress stimulation of inward rectifier potassium channels in Andersen-Tawil syndrome. The FASEB Journal 26, 513-522.
30. Cytoplasmic domain structures of Kir2.1 and Kir3.1 show sites for modulating gating and rectification. Nature neuroscience 8, 279-287.
31. Doherty GJ & McMahon HT. (2009). Mechanisms of endocytosis. Annual review of biochemistry 78, 857-902.
32. Nichols C & Lopatin A. (1997). Inward rectifier potassium channels. Annual Review of Physiology 59, 171-191.
33. Wischmeyer E, Döring F & Karschin A. (1998). Acute suppression of inwardly rectifying Kir2. 1 channels by direct tyrosine kinase phosphorylation. Journal of Biological Chemistry 273, 34063-34068.
34. Leonoudakis D, Conti LR, Radeke CM, McGuire LM & Vandenberg CA. (2004). A multiprotein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is associated with inward rectifier Kir2 potassium channels. The Journal of biological chemistry 279, 19051-19063.
35. Leyland ML & Dart C. (2004). An alternatively spliced isoform of PSD- 93/chapsyn 110 binds to the inwardly rectifying potassium channel, Kir2.1. The Journal of biological chemistry 279, 43427-43436.
36. Mason AK, Jacobs BE & Welling PA. (2008). AP-2-dependent internalization of potassium channel Kir2. 3 is driven by a novel di-hydrophobic signal. Journal of Biological Chemistry 283, 5973-5984.
37. Ho K, Nichols CG, Lederer WJ, Lytton J, Vassilev PM, Kanazirska MV & Hebert SC. (1993). Cloning and expression of an inwardly rectifying ATP- regulated potassium channel.
38. Kubo Y, Baldwin TJ, Jan YN & Jan LY. (1993). Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature 362, 127-133.
39. McMahon HT & Boucrot E. (2011). Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nature reviews Molecular cell biology 12, 517-533.
40. Preisig-Muller R, Schlichthorl G, Goerge T, Heinen S, Bruggemann A, Rajan S, Derst C, Veh RW & Daut J. (2002). Heteromerization of Kir2.x potassium channels contributes to the phenotype of Andersen's syndrome. Proceedings of the National Academy of Sciences of the United States of America 99, 7774-7779.
41. Heginbotham L, Lu Z, Abramson T & MacKinnon R. (1994). Mutations in the K+ channel signature sequence. Biophysical Journal 66, 1061-1067.
42. Groves B, Gong Q, Xu Z, Huntsman C, Nguyen C, Li D & Ma D. (2007). A specific role of AGS3 in the surface expression of plasma membrane proteins. Proceedings of the National Academy of Sciences 104, 18103- 18108.
43. Fang L, Garuti R, Kim B-Y, Wade JB & Welling PA. (2009). The ARH adaptor protein regulates endocytosis of the ROMK potassium secretory channel in mouse kidney. The Journal of clinical investigation 119, 3278-3289.
44. Anumonwo JM & Lopatin AN. (2010). Cardiac strong inward rectifier potassium channels. J Mol Cell Cardiol 48, 45-54.
45. Boyer SB, Slesinger PA & Jones SV. (2009). Regulation of Kir2.1 channels by the Rho-GTPase, Rac1. Journal of cellular physiology 218, 385-393.
46. Sorkin A & von Zastrow M. (2009). Endocytosis and signalling: intertwining molecular networks. Nature reviews Molecular cell biology 10, 609-622.
47. Ortega B, Mason AK & Welling PA. (2012). A Tandem Di-hydrophobic Motif Mediates Clathrin-dependent Endocytosis via Direct Binding to the AP-2 ασ2 Subunits. Journal of Biological Chemistry 287, 26867-26875.
48. Sandoz G & Levitz J. (2013). Optogenetic techniques for the study of native potassium channels. Frontiers in molecular neuroscience 6, 6.
49. Jansen JA, de Boer TP, Wolswinkel R, van Veen TA, Vos MA, van Rijen HV & van der Heyden MA. (2008). Lysosome mediated Kir2. 1 breakdown directly influences inward rectifier current density. Biochemical and biophysical research communications 367, 687-692.

Das Dokument ist im Internet frei zugänglich - Hinweise zu den Nutzungsrechten