The fully linked HTML version of this article has now been published.
JCS ePress
online publication date 26 Mar 2003
doi: 10.1242/jcs.00397
Research Article
Agonist-induced endocytosis of lysophosphatidic acid-coupled LPA1/EDG-2 receptors via a dynamin2- and Rab5-dependent pathway
Mandi M. Murph,
Launa A. Scaccia,
Laura A. Volpicelli,
and
Harish Radhakrishna*
* Author for correspondence (e-mail: harish.radhakrishna{at}biology.gatech.edu)
Lysophosphatidic acid (LPA) is a serum-borne phospholipid that exerts a pleiotropic range of effects on cells through activation of three closely related G-protein-coupled receptors termed LPA1/EDG-2, LPA2/EDG-4 and LPA3/EDG-7. Of these receptors, the LPA1 receptor is the most widely expressed. In this study, we investigated the agonist-induced endocytosis of the human LPA1 receptor, bearing an N-terminal FLAG epitope tag, in stably transfected HeLa cells. Treatment with LPA induced the rapid endocytosis of approximately 40% of surface LPA1 within 15 minutes. Internalization was both dose dependent and LPA specific since neither lysophophatidylcholine nor sphingosine-1-phosphate induced LPA1 endocytosis. Removal of agonist following 30 minutes incubation resulted in recycling of LPA1 back to the cell surface. LPA1 internalization was strongly inhibited by dominant-inhibitory mutants of both dynamin2 (K44A) and Rab5a (S34N). In addition, both dynamin2 K44A and Rab5 S34N mildly inhibited LPA1-dependent activation of serum response factor. Finally, our results also indicate that LPA1 exhibits basal, LPA-dependent internalization in the presence of serum-containing medium.
This article has been cited by other articles:
|
|
|
|
 
N. J. D. McLaughlin, A. Banerjee, S. Y. Khan, J. L. Lieber, M. R. Kelher, F. Gamboni-Robertson, F. R. Sheppard, E. E. Moore, G. W. Mierau, D. J. Elzi, et al.
Platelet-Activating Factor-Mediated Endosome Formation Causes Membrane Translocation of p67phox and p40phox That Requires Recruitment and Activation of p38 MAPK, Rab5a, and Phosphatidylinositol 3-Kinase in Human Neutrophils
J. Immunol.,
June 15, 2008;
180(12):
8192 - 8203.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. M. Urs, A. P. Kowalczyk, and H. Radhakrishna
Different Mechanisms Regulate Lysophosphatidic Acid (LPA)-dependent Versus Phorbol Ester-dependent Internalization of the LPA1 Receptor
J. Biol. Chem.,
February 29, 2008;
283(9):
5249 - 5257.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. G. Matteson, J. Desai, R. Korstanje, G. Lazar, T. E. Borsuk, J. Rollins, S. Kadambi, J. Joseph, T. Rahman, J. Wink, et al.
The orphan G protein-coupled receptor, Gpr161, encodes the vacuolated lens locus and controls neurulation and lens development
PNAS,
February 12, 2008;
105(6):
2088 - 2093.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Billon-Denis, Z. Tanfin, and P. Robin
Role of lysophosphatidic acid in the regulation of uterine leiomyoma cell proliferation by phospholipase D and autotaxin
J. Lipid Res.,
February 1, 2008;
49(2):
295 - 307.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Errasti-Murugarren, P. Cano-Soldado, M. Pastor-Anglada, and F. J. Casado
Functional Characterization of a Nucleoside-Derived Drug Transporter Variant (hCNT3C602R) Showing Altered Sodium-Binding Capacity
Mol. Pharmacol.,
February 1, 2008;
73(2):
379 - 386.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Murph, J. Hurst-Kennedy, V. Newton, D. N. Brindley, and H. Radhakrishna
Lysophosphatidic Acid Decreases the Nuclear Localization and Cellular Abundance of the p53 Tumor Suppressor in A549 Lung Carcinoma Cells
Mol. Cancer Res.,
November 1, 2007;
5(11):
1201 - 1211.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Uezu, A. Horiuchi, K. Kanda, N. Kikuchi, K. Umeda, K. Tsujita, S. Suetsugu, N. Araki, H. Yamamoto, T. Takenawa, et al.
SGIP1{alpha} Is an Endocytic Protein That Directly Interacts with Phospholipids and Eps15
J. Biol. Chem.,
September 7, 2007;
282(36):
26481 - 26489.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. T.-Y. Wong, C.-C. Hon, F. Zeng, and F. C.-C. Leung
Screening of differentially expressed transcripts in infectious bursal disease virus-induced apoptotic chicken embryonic fibroblasts by using cDNA microarrays
J. Gen. Virol.,
June 1, 2007;
88(6):
1785 - 1796.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Chen, L. N. Towers, and K. L. O'Connor
LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells
Am J Physiol Cell Physiol,
May 1, 2007;
292(5):
C1927 - C1933.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. M. Urs, K. T. Jones, P. D. Salo, J. E. Severin, J. Trejo, and H. Radhakrishna
A requirement for membrane cholesterol in the {beta}-arrestin- and clathrin-dependent endocytosis of LPA1 lysophosphatidic acid receptors
J. Cell Sci.,
November 15, 2005;
118(22):
5291 - 5304.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Wang, C. G. Radu, L. V. Yang, L. A. Bentolila, M. Riedinger, and O. N. Witte
Lysophosphatidylcholine-induced Surface Redistribution Regulates Signaling of the Murine G Protein-coupled Receptor G2A
Mol. Biol. Cell,
May 1, 2005;
16(5):
2234 - 2247.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2003
