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Neuropeptide Y receptor interactions regulate its mitogenic activity.
Neuropeptides. 2019 Feb; 73:11-24.N

Abstract

Neuropeptide Y (NPY) is a multifunctional neurotransmitter acting via G protein-coupled receptors - Y1R, Y2R and Y5R. NPY activities, such as its proliferative effects, are mediated by multiple receptors, which have the ability to dimerize. However, the role of this receptor interplay in NPY functions remains unclear. The goal of the current study was to identify NPY receptor interactions, focusing on the ligand-binding fraction, and determine their impact on the mitogenic activity of the peptide. Y1R, Y2R and Y5R expressed in CHO-K1 cells formed homodimers detectable on the cell surface by cross-linking. Moreover, Y1R and Y5R heterodimerized, while no Y2R/Y5R heterodimers were detected. Nevertheless, Y5R failed to block internalization of its cognate receptor in both Y1R/Y5R and Y2R/Y5R transfectants, indicating Y5R transactivation upon stimulation of the co-expressed receptor. These receptor interactions correlated with an augmented mitogenic response to NPY. In Y1R/Y5R and Y2R/Y5R transfectants, the proliferative response started at picomolar NPY concentrations, while nanomolar concentrations were needed to trigger proliferation in cells transfected with single receptors. Thus, our data identify direct and indirect heterotypic NPY receptor interactions as the mechanism amplifying its activity. Understanding these processes is crucial for the design of treatments targeting the NPY system.

Authors+Show Affiliations

Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC, USA.Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC, USA; New York Genome Center, New York, NY, USA.Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC, USA.Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC, USA.Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA.Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC, USA; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC, USA. Electronic address: jbk4@georgetown.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30503694

Citation

Czarnecka, Magdalena, et al. "Neuropeptide Y Receptor Interactions Regulate Its Mitogenic Activity." Neuropeptides, vol. 73, 2019, pp. 11-24.
Czarnecka M, Lu C, Pons J, et al. Neuropeptide Y receptor interactions regulate its mitogenic activity. Neuropeptides. 2019;73:11-24.
Czarnecka, M., Lu, C., Pons, J., Maheswaran, I., Ciborowski, P., Zhang, L., Cheema, A., & Kitlinska, J. (2019). Neuropeptide Y receptor interactions regulate its mitogenic activity. Neuropeptides, 73, 11-24. https://doi.org/10.1016/j.npep.2018.11.008
Czarnecka M, et al. Neuropeptide Y Receptor Interactions Regulate Its Mitogenic Activity. Neuropeptides. 2019;73:11-24. PubMed PMID: 30503694.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuropeptide Y receptor interactions regulate its mitogenic activity. AU - Czarnecka,Magdalena, AU - Lu,Congyi, AU - Pons,Jennifer, AU - Maheswaran,Induja, AU - Ciborowski,Pawel, AU - Zhang,Lihua, AU - Cheema,Amrita, AU - Kitlinska,Joanna, Y1 - 2018/11/27/ PY - 2018/05/17/received PY - 2018/10/15/revised PY - 2018/11/26/accepted PY - 2020/02/01/pmc-release PY - 2018/12/7/pubmed PY - 2019/2/12/medline PY - 2018/12/4/entrez KW - G protein-coupled receptors KW - Heterodimerization KW - Homodimerization KW - Neuropeptide Y KW - Proliferation SP - 11 EP - 24 JF - Neuropeptides JO - Neuropeptides VL - 73 N2 - Neuropeptide Y (NPY) is a multifunctional neurotransmitter acting via G protein-coupled receptors - Y1R, Y2R and Y5R. NPY activities, such as its proliferative effects, are mediated by multiple receptors, which have the ability to dimerize. However, the role of this receptor interplay in NPY functions remains unclear. The goal of the current study was to identify NPY receptor interactions, focusing on the ligand-binding fraction, and determine their impact on the mitogenic activity of the peptide. Y1R, Y2R and Y5R expressed in CHO-K1 cells formed homodimers detectable on the cell surface by cross-linking. Moreover, Y1R and Y5R heterodimerized, while no Y2R/Y5R heterodimers were detected. Nevertheless, Y5R failed to block internalization of its cognate receptor in both Y1R/Y5R and Y2R/Y5R transfectants, indicating Y5R transactivation upon stimulation of the co-expressed receptor. These receptor interactions correlated with an augmented mitogenic response to NPY. In Y1R/Y5R and Y2R/Y5R transfectants, the proliferative response started at picomolar NPY concentrations, while nanomolar concentrations were needed to trigger proliferation in cells transfected with single receptors. Thus, our data identify direct and indirect heterotypic NPY receptor interactions as the mechanism amplifying its activity. Understanding these processes is crucial for the design of treatments targeting the NPY system. SN - 1532-2785 UR - https://www.unboundmedicine.com/medline/citation/30503694/Neuropeptide_Y_receptor_interactions_regulate_its_mitogenic_activity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0143-4179(18)30096-9 DB - PRIME DP - Unbound Medicine ER -