Contact
Biomedical Research Center251 Bayview Boulevard
Suite 200
Baltimore, MD 21224
Education
Ph.D. - Anatomy - University of Puerto Rico, Medical Sciences Campus, San Juan, PR
B.S. - Industrial Biotechnology - University of Puerto Rico, Mayagüez Campus, Mayagüez, PR
Research Interests
Francheska Delgado-Peraza’s research focuses in uncovering the role of regulatory elements of the SNc dopamine neuron excitability in the development of motor symptoms in Huntington’s disease. She is interested in understanding the synaptic basis for excessive dopamine levels in early HD, by targeting SK and GIRK channel function in midbrain dopamine neurons. Her long-term goal is to play a central role on the development of potential therapies for HD.
Selected Publications
2016
Delgado-Peraza, Francheska; Ahn, Kwang H; Nogueras-Ortiz, Carlos; Mungrue, Imran N; Mackie, Ken; Kendall, Debra A; Yudowski, Guillermo A
Mechanisms of Biased beta-Arrestin-Mediated Signaling Downstream from the Cannabinoid 1 Receptor. Journal Article
In: Mol Pharmacol, vol. 89, no. 6, pp. 618–629, 2016, ISSN: 1521-0111 (Electronic); 0026-895X (Linking).
@article{Delgado-Peraza:2016aab,
title = {Mechanisms of Biased beta-Arrestin-Mediated Signaling Downstream from the Cannabinoid 1 Receptor.},
author = {Francheska Delgado-Peraza and Kwang H Ahn and Carlos Nogueras-Ortiz and Imran N Mungrue and Ken Mackie and Debra A Kendall and Guillermo A Yudowski},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27009233},
doi = {10.1124/mol.115.103176},
issn = {1521-0111 (Electronic); 0026-895X (Linking)},
year = {2016},
date = {2016-06-01},
journal = {Mol Pharmacol},
volume = {89},
number = {6},
pages = {618--629},
abstract = {Activation of G protein-coupled receptors results in multiple waves of signaling that are mediated by heterotrimeric G proteins and the scaffolding proteins beta-arrestin 1/2. Ligands can elicit full or subsets of cellular responses, a concept defined as ligand bias or functional selectivity. However, our current understanding of beta-arrestin-mediated signaling is still very limited. Here we provide a comprehensive view of beta-arrestin-mediated signaling from the cannabinoid 1 receptor (CB1R). By using a signaling biased receptor, we define the cascades, specific receptor kinases, and molecular mechanism underlying beta-arrestin-mediated signaling: We identify the interaction kinetics of CB1R and beta-arrestin 1 during their endocytic trafficking as directly proportional to its efficacy. Finally, we demonstrate that signaling results in the control of genes clustered around prosurvival and proapoptotic functions among others. Together, these studies constitute a comprehensive description of beta-arrestin-mediated signaling from CB1Rs and suggest modulation of receptor endocytic trafficking as a therapeutic approach to control beta-arrestin-mediated signaling.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Activation of G protein-coupled receptors results in multiple waves of signaling that are mediated by heterotrimeric G proteins and the scaffolding proteins beta-arrestin 1/2. Ligands can elicit full or subsets of cellular responses, a concept defined as ligand bias or functional selectivity. However, our current understanding of beta-arrestin-mediated signaling is still very limited. Here we provide a comprehensive view of beta-arrestin-mediated signaling from the cannabinoid 1 receptor (CB1R). By using a signaling biased receptor, we define the cascades, specific receptor kinases, and molecular mechanism underlying beta-arrestin-mediated signaling: We identify the interaction kinetics of CB1R and beta-arrestin 1 during their endocytic trafficking as directly proportional to its efficacy. Finally, we demonstrate that signaling results in the control of genes clustered around prosurvival and proapoptotic functions among others. Together, these studies constitute a comprehensive description of beta-arrestin-mediated signaling from CB1Rs and suggest modulation of receptor endocytic trafficking as a therapeutic approach to control beta-arrestin-mediated signaling.
Delgado-Peraza, Francheska; Nogueras-Ortiz, Carlos; Canabal, Agnes M Acevedo; Roman-Vendrell, Cristina; Yudowski, Guillermo A
Imaging GPCRs trafficking and signaling with total internal reflection fluorescence microscopy in cultured neurons. Journal Article
In: Methods Cell Biol, vol. 132, pp. 25–33, 2016, ISSN: 0091-679X (Print); 0091-679X (Linking).
@article{Delgado-Peraza:2016ab,
title = {Imaging GPCRs trafficking and signaling with total internal reflection fluorescence microscopy in cultured neurons.},
author = {Francheska Delgado-Peraza and Carlos Nogueras-Ortiz and Agnes M Acevedo Canabal and Cristina Roman-Vendrell and Guillermo A Yudowski},
url = {https://www.ncbi.nlm.nih.gov/pubmed/26928537},
doi = {10.1016/bs.mcb.2015.10.002},
issn = {0091-679X (Print); 0091-679X (Linking)},
year = {2016},
date = {2016-01-01},
journal = {Methods Cell Biol},
volume = {132},
pages = {25--33},
address = {Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, San Juan, PR, USA; Department of Anatomy and Neurobiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.},
abstract = {Total internal reflection fluorescence (TIRF) microscopy allows probing the cellular events occurring close and at the plasma membrane. Over the last decade, we have seen a significant increase in the number of publications applying TIRF microscopy to unravel some of the fundamental biological questions regarding G protein-coupled receptors (GPCRs) function such as the mechanisms controlling receptor trafficking, quaternary structure, and signaling among others. Most of the published work has been performed in heterologous systems such as HEK293 and CHO cells, where the imaging surface available is higher and smoother when compared with the narrow processes or the smaller cell bodies of neurons. However, some publications have expanded our understanding of these events to primary cell cultures, mostly rat hippocampal and striatal neuronal cultures. Results from these cells provide a bona fide model of the complex events controlling GPCR function in living cells. We believe more work needs to be performed in primary cultures and eventually in intact tissue to complement the knowledge obtained from heterologous cell models. Here, we described a step-by-step protocol to investigate the surface trafficking and signaling from GPCRs in rat hippocampal and striatal primary cultures.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Total internal reflection fluorescence (TIRF) microscopy allows probing the cellular events occurring close and at the plasma membrane. Over the last decade, we have seen a significant increase in the number of publications applying TIRF microscopy to unravel some of the fundamental biological questions regarding G protein-coupled receptors (GPCRs) function such as the mechanisms controlling receptor trafficking, quaternary structure, and signaling among others. Most of the published work has been performed in heterologous systems such as HEK293 and CHO cells, where the imaging surface available is higher and smoother when compared with the narrow processes or the smaller cell bodies of neurons. However, some publications have expanded our understanding of these events to primary cell cultures, mostly rat hippocampal and striatal neuronal cultures. Results from these cells provide a bona fide model of the complex events controlling GPCR function in living cells. We believe more work needs to be performed in primary cultures and eventually in intact tissue to complement the knowledge obtained from heterologous cell models. Here, we described a step-by-step protocol to investigate the surface trafficking and signaling from GPCRs in rat hippocampal and striatal primary cultures.
2015
Leung, Wilson; Shaffer, Christopher D; Reed, Laura K; Smith, Sheryl T; Barshop, William; Dirkes, William; Dothager, Matthew; Lee, Paul; Wong, Jeannette; Xiong, David; Delgado-Peraza, Franccheska
Drosophila muller f elements maintain a distinct set of genomic properties over 40 million years of evolution. Journal Article
In: G3 (Bethesda), vol. 5, no. 5, pp. 719–740, 2015, ISSN: 2160-1836 (Electronic); 2160-1836 (Linking).
@article{Leung:2015aab,
title = {Drosophila muller f elements maintain a distinct set of genomic properties over 40 million years of evolution.},
author = {Wilson Leung and Christopher D Shaffer and Laura K Reed and Sheryl T Smith and William Barshop and William Dirkes and Matthew Dothager and Paul Lee and Jeannette Wong and David Xiong and Franccheska Delgado-Peraza},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25740935},
doi = {10.1534/g3.114.015966},
issn = {2160-1836 (Electronic); 2160-1836 (Linking)},
year = {2015},
date = {2015-03-04},
journal = {G3 (Bethesda)},
volume = {5},
number = {5},
pages = {719--740},
address = {Department of Biology, Washington University in St. Louis, St. Louis, MO 63130.},
abstract = {The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.
2014
Roman-Vendrell, Cristina; Chevalier, Michael; Acevedo-Canabal, Agnes M; Delgado-Peraza, Francheska; Flores-Otero, Jacqueline; Yudowski, Guillermo A
Imaging of kiss-and-run exocytosis of surface receptors in neuronal cultures. Journal Article
In: Front Cell Neurosci, vol. 8, pp. 363, 2014, ISSN: 1662-5102 (Print); 1662-5102 (Linking).
@article{Roman-Vendrell:2014aa,
title = {Imaging of kiss-and-run exocytosis of surface receptors in neuronal cultures.},
author = {Cristina Roman-Vendrell and Michael Chevalier and Agnes M Acevedo-Canabal and Francheska Delgado-Peraza and Jacqueline Flores-Otero and Guillermo A Yudowski},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25404895},
doi = {10.3389/fncel.2014.00363},
issn = {1662-5102 (Print); 1662-5102 (Linking)},
year = {2014},
date = {2014-11-03},
journal = {Front Cell Neurosci},
volume = {8},
pages = {363},
address = {Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus San Juan, PR, USA ; Department of Physiology, School of Medicine, University of Puerto Rico San Juan, PR, USA.},
abstract = {Transmembrane proteins are continuously shuttled from the endosomal compartment to the neuronal plasma membrane by highly regulated and complex trafficking steps. These events are involved in many homeostatic and physiological processes such as neuronal growth, signaling, learning and memory among others. We have previously shown that endosomal exocytosis of the B2 adrenergic receptor (B2AR) and the GluR1-containing AMPA receptor to the neuronal plasma membrane is mediated by two different types of vesicular fusion. A rapid type of exocytosis in which receptors are delivered to the plasma membrane in a single kinetic step, and a persistent mode in which receptors remain clustered at the insertion site for a variable period of time before delivery to the cell surface. Here, by comparing the exocytosis of multiple receptors in dissociated hippocampal and striatal cultures, we show that persistent events are a general mechanism of vesicular delivery. Persistent events were only observed after 10 days in vitro, and their frequency increased with use of the calcium ionophore A23187 and with depolarization induced by KCl. Finally, we determined that vesicles producing persistent events remain at the plasma membrane, closing and reopening their fusion pore for a consecutive release of cargo in a mechanism reminiscent of synaptic kiss-and-run. These results indicate that the delivery of transmembrane receptors to the cell surface can be dynamically regulated by kiss-and-run exocytosis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Transmembrane proteins are continuously shuttled from the endosomal compartment to the neuronal plasma membrane by highly regulated and complex trafficking steps. These events are involved in many homeostatic and physiological processes such as neuronal growth, signaling, learning and memory among others. We have previously shown that endosomal exocytosis of the B2 adrenergic receptor (B2AR) and the GluR1-containing AMPA receptor to the neuronal plasma membrane is mediated by two different types of vesicular fusion. A rapid type of exocytosis in which receptors are delivered to the plasma membrane in a single kinetic step, and a persistent mode in which receptors remain clustered at the insertion site for a variable period of time before delivery to the cell surface. Here, by comparing the exocytosis of multiple receptors in dissociated hippocampal and striatal cultures, we show that persistent events are a general mechanism of vesicular delivery. Persistent events were only observed after 10 days in vitro, and their frequency increased with use of the calcium ionophore A23187 and with depolarization induced by KCl. Finally, we determined that vesicles producing persistent events remain at the plasma membrane, closing and reopening their fusion pore for a consecutive release of cargo in a mechanism reminiscent of synaptic kiss-and-run. These results indicate that the delivery of transmembrane receptors to the cell surface can be dynamically regulated by kiss-and-run exocytosis.
Flores-Otero, Jacqueline; Ahn, Kwang H; Delgado-Peraza, Francheska; Mackie, Ken; Kendall, Debra A; Yudowski, Guillermo A
Ligand-specific endocytic dwell times control functional selectivity of the cannabinoid receptor 1. Journal Article
In: Nat Commun, vol. 5, pp. 4589, 2014, ISSN: 2041-1723 (Electronic); 2041-1723 (Linking).
@article{Flores-Otero:2014aa,
title = {Ligand-specific endocytic dwell times control functional selectivity of the cannabinoid receptor 1.},
author = {Jacqueline Flores-Otero and Kwang H Ahn and Francheska Delgado-Peraza and Ken Mackie and Debra A Kendall and Guillermo A Yudowski},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25081814},
doi = {10.1038/ncomms5589},
issn = {2041-1723 (Electronic); 2041-1723 (Linking)},
year = {2014},
date = {2014-08-01},
journal = {Nat Commun},
volume = {5},
pages = {4589},
address = {1$]$ Department of Anatomy and Neurobiology, University of Puerto Rico, Medical Sciences Campus, PO Box 365067, San Juan 00936, Puerto Rico [2].},
abstract = {G protein-coupled receptors (GPCRs) are the major transducers of external stimuli and key therapeutic targets in many pathological conditions. When activated by different ligands, one receptor can elicit multiple signalling cascades that are mediated by G proteins or beta-arrestin, a process defined as functional selectivity or ligand bias. However, the dynamic mechanisms underlying beta-arrestin signalling remain unknown. Here by studying the cannabinoid receptor 1 (CB1R), we identify ligand-specific endocytic dwell times, that is, the time during which receptors are clustered into clathrin pits together with beta-arrestins before endocytosis, as the mechanism controlling beta-arrestin signalling. Agonists inducing short endocytic dwell times produce little or no beta-arrestin signalling, whereas those eliciting prolonged dwell times induce robust signalling. Remarkably, extending CB1R dwell times by preventing endocytosis substantially increased beta-arrestin signalling. These studies reveal how receptor activation translates into beta-arrestin signalling and identify a mechanism to control this pathway.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
G protein-coupled receptors (GPCRs) are the major transducers of external stimuli and key therapeutic targets in many pathological conditions. When activated by different ligands, one receptor can elicit multiple signalling cascades that are mediated by G proteins or beta-arrestin, a process defined as functional selectivity or ligand bias. However, the dynamic mechanisms underlying beta-arrestin signalling remain unknown. Here by studying the cannabinoid receptor 1 (CB1R), we identify ligand-specific endocytic dwell times, that is, the time during which receptors are clustered into clathrin pits together with beta-arrestins before endocytosis, as the mechanism controlling beta-arrestin signalling. Agonists inducing short endocytic dwell times produce little or no beta-arrestin signalling, whereas those eliciting prolonged dwell times induce robust signalling. Remarkably, extending CB1R dwell times by preventing endocytosis substantially increased beta-arrestin signalling. These studies reveal how receptor activation translates into beta-arrestin signalling and identify a mechanism to control this pathway.
