|
|
|
|
|
||
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
Research Article |
1 Department of Physiology, University of Saarland, D-66421 Homburg,
Germany
2 Department of Clinical Pharmacology, University of Bern, Murtenstrasse 35,
3010 Bern, Switzerland
3 Department of Geriatrics, Geneva University Hospital, CH-1211 Geneva 14,
Switzerland
* Author for correspondence (e-mail: phlmery{at}uniklinik-saarland.de)
Accepted 14 June 2002
Mammalian homologs of the Drosophila TRP protein have been shown to form cation-permeable channels in the plasma membrane but very little is known about the mechanisms that control their cell surface localization. Recently it has been demonstrated that the last three C-terminal amino acids (TRL) of TRPC4 comprise a PDZ-interacting domain that binds to the scaffold protein EBP50 [ezrin/moesin/radixin-binding phosphoprotein 50]. In this report, we have examined the influence of the TRL motif on the subcellular distribution of TRPC4 in human embryonic kidney (HEK) 293 cells. We have also analyzed the consequences of the interaction between EBP50 and the membrane-cytoskeletal adaptors of the ezrin/radixin/moesin (ERM) family for the cell surface expression of TRPC4. Using immunofluorescence microscopy, we found that the mutant lacking the TRL motif accumulated into cell outgrowths and exhibited a punctate distribution pattern whereas the wild-type channel was evenly distributed on the cell surface. Deletion of the PDZ-interacting domain also decreased the expression of TRPC4 in the plasma membrane by 2.4-fold, as assessed by cell surface biotinylation experiments. Finally, in a large percentage of cells co-expressing TRPC4 and an EBP50 mutant lacking the ERM-binding site, TRPC4 was not present in the plasma membrane but co-localized with the truncated scaffold in a perinuclear compartment (most probably representing the Golgi apparatus) and in vesicles associated with actin filaments. Our data demonstrate that the PDZ-interacting domain of TRPC4 controls its localization and surface expression in transfected HEK293 cells. They also point to a yet unexplored role of the EBP50-ERM complex in the regulation of protein insertion into the plasma membrane.
Key words: TRPC proteins, PDZ domain, EBP50, Membrane localization
This article has been cited by other articles:
|
|
 |
|
  K.-i. Otsuguro, J. Tang, Y. Tang, R. Xiao, M. Freichel, V. Tsvilovskyy, S. Ito, V. Flockerzi, M. X. Zhu, and A. V. Zholos Isoform-specific Inhibition of TRPC4 Channel by Phosphatidylinositol 4,5-Bisphosphate J. Biol. Chem., April 11, 2008; 283(15): 10026 - 10036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. Odell, D. F. Van Helden, and J. L. Scott The Spectrin Cytoskeleton Influences the Surface Expression and Activation of Human Transient Receptor Potential Channel 4 Channels J. Biol. Chem., February 15, 2008; 283(7): 4395 - 4407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Cardone, A. Bellizzi, G. Busco, E. J. Weinman, M. E. Dell'Aquila, V. Casavola, A. Azzariti, A. Mangia, A. Paradiso, and S. J. Reshkin The NHERF1 PDZ2 Domain Regulates PKA-RhoA-p38-mediated NHE1 Activation and Invasion in Breast Tumor Cells Mol. Biol. Cell, May 1, 2007; 18(5): 1768 - 1780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.K.M. Mahbub Hasan, Z. Ou, K. Sakakibara, S. Hirahara, T. Iwasaki, K.-i. Sato, and Y. Fukami Characterization of Xenopus egg membrane microdomains containing uroplakin Ib/III complex: roles of their molecular interactions for subcellular localization and signal transduction. Genes Cells, February 1, 2007; 12(2): 251 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Erler, D. M. M. Al-Ansary, U. Wissenbach, T. F. J. Wagner, V. Flockerzi, and B. A. Niemeyer Trafficking and Assembly of the Cold-sensitive TRPM8 Channel J. Biol. Chem., December 15, 2006; 281(50): 38396 - 38404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Mazzochi, D. J. Benos, and P. R. Smith Interaction of epithelial ion channels with the actin-based cytoskeleton Am J Physiol Renal Physiol, December 1, 2006; 291(6): F1113 - F1122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. V. Remillard and J. X.-J. Yuan Transient Receptor Potential Channels and Caveolin-1: Good Friends in Tight Spaces Mol. Pharmacol., October 1, 2006; 70(4): 1151 - 1154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xu, Y. Fu, W. Tian, and D. M. Cohen Glycosylation of the osmoresponsive transient receptor potential channel TRPV4 on Asn-651 influences membrane trafficking Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1103 - F1109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Cioffi, S. Wu, M. Alexeyev, S. R. Goodman, M. X. Zhu, and T. Stevens Activation of the Endothelial Store-Operated ISOC Ca2+ Channel Requires Interaction of Protein 4.1 With TRPC4 Circ. Res., November 25, 2005; 97(11): 1164 - 1172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. Odell, J. L. Scott, and D. F. Van Helden Epidermal Growth Factor Induces Tyrosine Phosphorylation, Membrane Insertion, and Activation of Transient Receptor Potential Channel 4 J. Biol. Chem., November 11, 2005; 280(45): 37974 - 37987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Chorna-Ornan, V. Tzarfaty, G. Ankri-Eliahoo, T. Joel-Almagor, N. E. Meyer, A. Huber, F. Payre, and B. Minke Light-regulated interaction of Dmoesin with TRP and TRPL channels is required for maintenance of photoreceptors J. Cell Biol., October 10, 2005; 171(1): 143 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Zhu, M. Chae, H. J. Kim, Y. M. Lee, M. J. Kim, N. G. Jin, D. K. Yang, I. So, and K. W. Kim Desensitization of canonical transient receptor potential channel 5 by protein kinase C Am J Physiol Cell Physiol, September 1, 2005; 289(3): C591 - C600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Aarts and M. Tymianski TRPM7 and Ischemic CNS Injury Neuroscientist, April 1, 2005; 11(2): 116 - 123. [Abstract] [PDF]
|
|
|
|
|
|
W. Lee-Kwon, J. B. Wade, Z. Zhang, T. L. Pallone, and E. J. Weinman Expression of TRPC4 channel protein that interacts with NHERF-2 in rat descending vasa recta Am J Physiol Cell Physiol, April 1, 2005; 288(4): C942 - C949. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Montell The TRP Superfamily of Cation Channels Sci. Signal., February 22, 2005; 2005(272): re3 - re3. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Erler, D. Hirnet, U. Wissenbach, V. Flockerzi, and B. A. Niemeyer Ca2+-selective Transient Receptor Potential V Channel Architecture and Function Require a Specific Ankyrin Repeat J. Biol. Chem., August 13, 2004; 279(33): 34456 - 34463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Howell, C. Borchers, and S. L. Milgram Heterogeneous Nuclear Ribonuclear Protein U Associates with YAP and Regulates Its Co-activation of Bax Transcription J. Biol. Chem., June 18, 2004; 279(25): 26300 - 26306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Mahon and G. V. Segre Stimulation by Parathyroid Hormone of a NHERF-1-assembled Complex Consisting of the Parathyroid Hormone I Receptor, Phospholipase C{beta}, and Actin Increases Intracellular Calcium in Opossum Kidney Cells J. Biol. Chem., May 28, 2004; 279(22): 23550 - 23558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Mao, E. Seidlitz, K. Ghosh, Y. Murakami, and H. P. Ghosh The Cytoplasmic Domain Is Critical to the Tumor Suppressor Activity of TSLC1 in Non-Small Cell Lung Cancer Cancer Res., November 15, 2003; 63(22): 7979 - 7985. [Abstract] [Full Text] [PDF]
|
|
