Phorbol esters increase dopamine transporter phosphorylation and decrease transport Vmax - PubMed (original) (raw)
Phorbol esters increase dopamine transporter phosphorylation and decrease transport Vmax
R A Huff et al. J Neurochem. 1997 Jan.
Free article
Abstract
Sodium- and chloride-coupled transport of dopamine from synapses into presynaptic terminals plays a key role in terminating dopaminergic neurotransmission. Regulation of the function of the dopamine transporter, the molecule responsible for this translocation, is thus of interest. The primary sequence of the dopamine transporter contains multiple potential phosphorylation sites, suggesting that the function of the transporter could be regulated by phosphorylation. Previous work from this laboratory has documented that phorbol ester activation of protein kinase C (PKC) decreases dopamine transport Vmax in transiently expressing COS cells. In the present report, we document in vivo phosphorylation of the rat dopamine transporter stably expressed in LLC-PK1, cells and show that phosphorylation is increased threefold by phorbol esters. Dopamine uptake is also regulated by phorbol esters in these cells; phorbol 12-myristate 13-acetate (PMA) reduces transport Vmax by 35%. Parallels between the time course, concentration dependency, and staurosporine sensitivity of alterations in transporter phosphorylation and transporter Vmax suggest that dopamine transporter phosphorylation involving PKC could contribute to this decreased transporter function. Phosphorylation of the dopamine transporter by PKC or by a PKC-activated kinase could be involved in rapid neuroadaptive processes in dopaminergic neurons.
Similar articles
- Protein kinase-mediated bidirectional trafficking and functional regulation of the human dopamine transporter.
Pristupa ZB, McConkey F, Liu F, Man HY, Lee FJ, Wang YT, Niznik HB. Pristupa ZB, et al. Synapse. 1998 Sep;30(1):79-87. doi: 10.1002/(SICI)1098-2396(199809)30:1<79::AID-SYN10>3.0.CO;2-K. Synapse. 1998. PMID: 9704884 - Protein kinase C-mediated functional regulation of dopamine transporter is not achieved by direct phosphorylation of the dopamine transporter protein.
Chang MY, Lee SH, Kim JH, Lee KH, Kim YS, Son H, Lee YS. Chang MY, et al. J Neurochem. 2001 May;77(3):754-61. doi: 10.1046/j.1471-4159.2001.00284.x. J Neurochem. 2001. PMID: 11331404 - Regulated trafficking of the human dopamine transporter. Clathrin-mediated internalization and lysosomal degradation in response to phorbol esters.
Daniels GM, Amara SG. Daniels GM, et al. J Biol Chem. 1999 Dec 10;274(50):35794-801. doi: 10.1074/jbc.274.50.35794. J Biol Chem. 1999. PMID: 10585462 - Regulation of the functional activity of the human dopamine transporter by protein kinase C.
Zhang L, Coffey LL, Reith ME. Zhang L, et al. Biochem Pharmacol. 1997 Mar 7;53(5):677-88. doi: 10.1016/s0006-2952(96)00898-2. Biochem Pharmacol. 1997. PMID: 9113087 - Phorbol esters alter functions of the expressed dopamine transporter.
Kitayama S, Dohi T, Uhl GR. Kitayama S, et al. Eur J Pharmacol. 1994 Jul 15;268(2):115-9. doi: 10.1016/0922-4106(94)90180-5. Eur J Pharmacol. 1994. PMID: 7957633
Cited by
- Dopamine transporter membrane mobility is bidirectionally regulated by phosphorylation and palmitoylation.
Shetty M, Bolland DE, Morrell J, Grove BD, Foster JD, Vaughan RA. Shetty M, et al. Curr Res Physiol. 2023 Sep 29;6:100106. doi: 10.1016/j.crphys.2023.100106. eCollection 2023. Curr Res Physiol. 2023. PMID: 38107792 Free PMC article. Review. - Overview of the structure and function of the dopamine transporter and its protein interactions.
Nepal B, Das S, Reith ME, Kortagere S. Nepal B, et al. Front Physiol. 2023 Mar 3;14:1150355. doi: 10.3389/fphys.2023.1150355. eCollection 2023. Front Physiol. 2023. PMID: 36935752 Free PMC article. Review. - Regulation of Glutamate, GABA and Dopamine Transporter Uptake, Surface Mobility and Expression.
Ryan RM, Ingram SL, Scimemi A. Ryan RM, et al. Front Cell Neurosci. 2021 Apr 13;15:670346. doi: 10.3389/fncel.2021.670346. eCollection 2021. Front Cell Neurosci. 2021. PMID: 33927596 Free PMC article. Review. - Prolyl Oligopeptidase Regulates Dopamine Transporter Oligomerization and Phosphorylation in a PKC- and ERK-Independent Manner.
Julku UH, Jäntti M, Svarcbahs R, Myöhänen TT. Julku UH, et al. Int J Mol Sci. 2021 Feb 10;22(4):1777. doi: 10.3390/ijms22041777. Int J Mol Sci. 2021. PMID: 33579026 Free PMC article. - In Situ Regulated Dopamine Transporter Trafficking: There's No Place Like Home.
Fagan RR, Kearney PJ, Melikian HE. Fagan RR, et al. Neurochem Res. 2020 Jun;45(6):1335-1343. doi: 10.1007/s11064-020-03001-6. Epub 2020 Mar 7. Neurochem Res. 2020. PMID: 32146647 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources