The receptor tyrosine kinase EPHB6 regulates catecholamine exocytosis in adrenal gland chromaffin cells.
Adrenal Glands
/ cytology
Animals
Catecholamines
/ genetics
Chromaffin Cells
/ cytology
Ephrin-B1
/ genetics
Exocytosis
Female
Male
Mice
Mice, Knockout
Microfilament Proteins
/ genetics
Mixed Function Oxygenases
/ genetics
Proto-Oncogene Mas
Proto-Oncogene Proteins c-fyn
/ genetics
Receptor, EphB6
/ genetics
Sex Characteristics
Signal Transduction
rhoA GTP-Binding Protein
/ genetics
EPHB6
F-actin
actin
adrenal
adrenal gland chromaffin cell
catecholamine
exocytosis
receptor tyrosine kinase
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
29 05 2020
29 05 2020
Historique:
received:
28
02
2020
revised:
20
04
2020
pubmed:
24
4
2020
medline:
29
12
2020
entrez:
24
4
2020
Statut:
ppublish
Résumé
The erythropoietin-producing human hepatocellular receptor EPH receptor B6 (EPHB6) is a receptor tyrosine kinase that has been shown previously to control catecholamine synthesis in the adrenal gland chromaffin cells (AGCCs) in a testosterone-dependent fashion. EPHB6 also has a role in regulating blood pressure, but several facets of this regulation remain unclear. Using amperometry recordings, we now found that catecholamine secretion by AGCCs is compromised in the absence of EPHB6. AGCCs from male knockout (KO) mice displayed reduced cortical F-actin disassembly, accompanied by decreased catecholamine secretion through exocytosis. This phenotype was not observed in AGCCs from female KO mice, suggesting that testosterone, but not estrogen, contributes to this phenotype. Of note, reverse signaling from EPHB6 to ephrin B1 (EFNB1) and a 7-amino acid-long segment in the EFNB1 intracellular tail were essential for the regulation of catecholamine secretion. Further downstream, the Ras homolog family member A (RHOA) and FYN proto-oncogene Src family tyrosine kinase (FYN)-proto-oncogene c-ABL-microtubule-associated monooxygenase calponin and LIM domain containing 1 (MICAL-1) pathways mediated the signaling from EFNB1 to the defective F-actin disassembly. We discuss the implications of EPHB6's effect on catecholamine exocytosis and secretion for blood pressure regulation.
Identifiants
pubmed: 32321761
pii: S0021-9258(17)49457-9
doi: 10.1074/jbc.RA120.013251
pmc: PMC7261780
doi:
Substances chimiques
Catecholamines
0
Efnb1 protein, mouse
0
Ephb6 protein, mouse
0
Ephrin-B1
0
MAS1 protein, human
0
Microfilament Proteins
0
Proto-Oncogene Mas
0
Receptor, EphB6
0
Mical1 protein, mouse
EC 1.-
Mixed Function Oxygenases
EC 1.-
Fyn protein, mouse
EC 2.7.10.2
Proto-Oncogene Proteins c-fyn
EC 2.7.10.2
RhoA protein, mouse
EC 3.6.5.2
rhoA GTP-Binding Protein
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7653-7668Subventions
Organisme : CIHR
ID : MOP272014
Pays : Canada
Informations de copyright
© 2020 Shi et al.
Déclaration de conflit d'intérêts
Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article.
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