Saber UCV
Repositorio Institucional
Repositorio Institucional
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https://saber.ucv.ve/handle/10872/18363
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| Title: | Is the activity of CGRP and Adrenomedullin regulated by RAMP (-2) and (-3) in Trypanosomatidae? An in-silico approach. |
| Authors: | Febres, Anthony Vanegas, Oriana Gianmmaressi, Michelle Gomes, Carlos Diaz, Emilia Ponte-Sucre, Alicia |
| Keywords: | Leishmania adrenomesullin calcitonin-like receptor calcitonin gene related peptide chemotatcit response receptor activity modifier protein |
| Issue Date: | 1-May-2018 |
| Series/Report no.: | Infect Genet Evol. 2018;61:197-206. doi: 10.1016/j.meegid.2018.04.003 |
| Abstract: | The Calcitonin-Like Receptor (CLR) belongs to the classical seven-transmembrane segment molecules coupled to heterotrimeric G proteins. Its pharmacology depends on the simultaneous expression of the so-called Receptor Activity Modifier Proteins (RAMP-) -1, -2 and -3. RAMP-associated proteins modulate glycosylation and cellular traffic of CLR, therefore determining its pharmacodynamics. In higher eukaryotes, the complex formed by CLR and RAMP-1 is more akin to bind Calcitonin Gene-Related Peptide (CGRP), whereas those formed by CLR and RAMP-2 or RAMP-3, bind preferentially Adrenomedullin (AM). In lower eukaryotes, RAMPs, or any homologous protein, have not been identified until now. Herein we demonstrated a negative chemotactic response elicited by CGRP (10-9 and 10-8 M) and AM (10-9 to 10-5 M). Whether or not this response is receptor mediated should be verified, as well as the expression of a 24 kDa band in Leishmania, recognized by western blot analysis by the use of (human-)-RAMP-2 antibodies as detection probes. Queries with human RAMP-2 and RAMP-3 protein sequences in blastp against Leishmania (Viannia) braziliensis predicted proteome, allowed us to detect two sequence alignments in the parasite: A RAMP-2-aligned sequence corresponding to Leishmania folylpolyglutamate synthase (FPGS), and a RAMP-3 aligned protein, a hypothetical Leishmania protein with yet unknown function. The presence of homologous of these proteins was described in-silico in other members of the Trypanosomatidae. These preliminary and not yet complete data suggest the feasibility that both CGRP and Adrenomedullin activities may be regulated by homologues of RAMP- (-2) and (-3) in these parasites. |
| URI: | http://hdl.handle.net/10872/18363 |
| ISSN: | 1567-1348 |
| Appears in Collections: | Artículos Publicados |
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