Is the activity of CGRP and Adrenomedullin regulated by RAMP (-2) and (-3) in Trypanosomatidae? An in-silico approach.
Infect Genet Evol
; 61: 197-206, 2018 07.
Article
em En
| MEDLINE
| ID: mdl-29626675
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 10-8â¯M) and AM (10-9 to 10-5â¯M). Whether or not this response is receptor mediated should be verified, as well as the expression of a 24â¯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 homologs of RAMP- (-2) and (-3) in these parasites.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeo Relacionado com Gene de Calcitonina
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Adrenomedulina
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Proteína 2 Modificadora da Atividade de Receptores
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Proteína 3 Modificadora da Atividade de Receptores
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Leishmania
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Infect Genet Evol
Assunto da revista:
BIOLOGIA
/
DOENCAS TRANSMISSIVEIS
/
GENETICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Venezuela
País de publicação:
Holanda