Dynamin and beta-arrestin reveal distinct mechanisms for G protein-coupled receptor internalization - PubMed (original) (raw)
. 1996 Aug 2;271(31):18302-5.
doi: 10.1074/jbc.271.31.18302.
Affiliations
- PMID: 8702465
- DOI: 10.1074/jbc.271.31.18302
Free article
Dynamin and beta-arrestin reveal distinct mechanisms for G protein-coupled receptor internalization
J Zhang et al. J Biol Chem. 1996.
Free article
Abstract
The process of agonist-promoted internalization (sequestration) of G protein-coupled receptors (GPCRs) is intimately linked to the regulation of GPCR responsiveness. Following agonist-mediated desensitization, sequestration of GPCR is presumably associated with the dephosphorylation and recycling of functional receptors. However, the exact mechanisms responsible for GPCR sequestration, even for the prototypic beta2-adrenergic receptor (beta2AR), have remained controversial. We demonstrate here that dynamin, a GTPase that regulates the formation and internalization of clathrin-coated vesicles, is essential for the agonist-promoted sequestration of the beta2AR, suggesting that the beta2AR internalizes via the clathrin-coated vesicle-mediated endocytic pathway. In contrast, internalization of the angiotensin II type 1A receptor (AT1AR), another typical GPCR, does not require dynamin. In addition, the AT1AR internalizes independent of the function of beta-arrestin, a critical component for beta2AR cellular trafficking, but additional AT1ARs are mobilized to the dynamin-dependent pathway upon overexpression of beta-arrestin. These findings demonstrate that GPCRs can utilize distinct endocytic pathways, distinguishable by dynamin and beta-arrestin, and that beta-arrestins function as adaptor proteins specifically targeting GPCRs for dynamin-dependent endocytosis via clathrin-coated vesicles.
Similar articles
- Receptor/beta-arrestin complex formation and the differential trafficking and resensitization of beta2-adrenergic and angiotensin II type 1A receptors.
Anborgh PH, Seachrist JL, Dale LB, Ferguson SS. Anborgh PH, et al. Mol Endocrinol. 2000 Dec;14(12):2040-53. doi: 10.1210/mend.14.12.0565. Mol Endocrinol. 2000. PMID: 11117533 - Properties of secretin receptor internalization differ from those of the beta(2)-adrenergic receptor.
Walker JK, Premont RT, Barak LS, Caron MG, Shetzline MA. Walker JK, et al. J Biol Chem. 1999 Oct 29;274(44):31515-23. doi: 10.1074/jbc.274.44.31515. J Biol Chem. 1999. PMID: 10531354 - Mechanisms and functions of AT(1) angiotensin receptor internalization.
Hunyady L, Catt KJ, Clark AJ, Gáborik Z. Hunyady L, et al. Regul Pept. 2000 Jul 28;91(1-3):29-44. doi: 10.1016/s0167-0115(00)00137-3. Regul Pept. 2000. PMID: 10967200 Review. - Molecular mechanisms of G protein-coupled receptor desensitization and resensitization.
Ferguson SS, Zhang J, Barak LS, Caron MG. Ferguson SS, et al. Life Sci. 1998;62(17-18):1561-5. doi: 10.1016/s0024-3205(98)00107-6. Life Sci. 1998. PMID: 9585136 Review.
Cited by
- ACKR3 Proximity Labeling Identifies Novel G protein- and β-arrestin-independent GPCR Interacting Proteins.
Hicks C, Gardner J, Eiger DS, Camarda ND, Pham U, Dhar S, Rodriguez H, Chundi A, Rajagopal S. Hicks C, et al. bioRxiv [Preprint]. 2024 Jan 28:2024.01.27.577545. doi: 10.1101/2024.01.27.577545. bioRxiv. 2024. PMID: 38410489 Free PMC article. Preprint. - The multifaceted functions of β-arrestins and their therapeutic potential in neurodegenerative diseases.
Kee TR, Khan SA, Neidhart MB, Masters BM, Zhao VK, Kim YK, McGill Percy KC, Woo JA. Kee TR, et al. Exp Mol Med. 2024 Feb;56(1):129-141. doi: 10.1038/s12276-023-01144-4. Epub 2024 Jan 11. Exp Mol Med. 2024. PMID: 38212557 Free PMC article. Review. - S-nitrosylation is required for β2AR desensitization and experimental asthma.
Fonseca FV, Raffay TM, Xiao K, McLaughlin PJ, Qian Z, Grimmett ZW, Adachi N, Wang B, Hausladen A, Cobb BA, Zhang R, Hess DT, Gaston B, Lambert NA, Reynolds JD, Premont RT, Stamler JS. Fonseca FV, et al. Mol Cell. 2022 Aug 18;82(16):3089-3102.e7. doi: 10.1016/j.molcel.2022.06.033. Epub 2022 Aug 4. Mol Cell. 2022. PMID: 35931084 Free PMC article. - A single phenylalanine residue in β-arrestin2 critically regulates its binding to G protein-coupled receptors.
Jean-Charles PY, Rajiv V, Sarker S, Han S, Bai Y, Masoudi A, Shenoy SK. Jean-Charles PY, et al. J Biol Chem. 2022 May;298(5):101837. doi: 10.1016/j.jbc.2022.101837. Epub 2022 Mar 17. J Biol Chem. 2022. PMID: 35307348 Free PMC article. - β-Arrestin-Biased Agonist Targeting the Brain AT1R (Angiotensin II Type 1 Receptor) Increases Aversion to Saline and Lowers Blood Pressure in Deoxycorticosterone Acetate-Salt Hypertension.
Zanaty M, Seara FAC, Nakagawa P, Deng G, Mathieu NM, Balapattabi K, Karnik SS, Grobe JL, Sigmund CD. Zanaty M, et al. Hypertension. 2021 Feb;77(2):420-431. doi: 10.1161/HYPERTENSIONAHA.120.15793. Epub 2020 Nov 30. Hypertension. 2021. PMID: 33249862 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources