title: Chromogranins A and B are key proteins in amine accumulation, but the catecholamine secretory pathway is conserved without them.
abstract: Chromogranins are the main soluble proteins in the large dense core secretory vesicles (LDCVs) found in aminergic neurons and chromaffin cells. We recently demonstrated that chromogranins A and B each regulate the concentration of adrenaline in chromaffin granules and its exocytosis. Here we have further studied the role played by these proteins by generating mice lacking both chromogranins. Surprisingly, these animals are both viable and fertile. Although chromogranins are thought to be essential for their biogenesis, LDCVs were evident in these mice. These vesicles do have a somewhat atypical appearance and larger size. Despite their increased size, single-cell amperometry recordings from chromaffin cells showed that the amine content in these vesicles is reduced by half. These data demonstrate that although chromogranins regulate the amine concentration in LDCVs, they are not completely essential, and other proteins unrelated to neurosecretion, such as fibrinogen, might compensate for their loss to ensure that vesicles are generated and the secretory pathway conserved.
authors: Unidad de Farmacología, Universidad de La Laguna, La Laguna, Tenerife, Spain.
authors: Jésica
authors: J
authors: Díaz-Vera
authors: Marcial
authors: M
authors: Camacho
authors: José David
authors: JD
authors: Machado
authors: Natalia
authors: N
authors: Domínguez
authors: Mónica S
authors: MS
authors: Montesinos
authors: Juan R
authors: JR
authors: Hernández-Fernaud
authors: Rafael
authors: R
authors: Luján
authors: Ricardo
authors: R
authors: Borges
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000502:physiology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D053379:Chromogranin A / Q000235:genetics* / Q000378:metabolism; D053378:Chromogranin B / Q000235:genetics* / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D005260:Female; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011247:Pregnancy; D055571:Secretory Pathway / Q000187:drug effects / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D002395:Catecholamines; D053379:Chromogranin A; D053378:Chromogranin B; D015259:Dopamine Agents; C506155:chromogranin A, mouse; C506137:chromogranin B, mouse; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase