An Alternative Exon of CAPS2 Influences Catecholamine Loading into LDCVs of Chromaffin Cells
| Autor: | Gudrun Ahnert-Hilger, Irene Brunk, David R. Stevens, Elvin Rajabov, Claudia Schirra, Olga Ratai, Ute Becherer, Jens Rettig, Praneeth Chitirala |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Serotonin Serotonin uptake Chromaffin Cells Nerve Tissue Proteins CHO Cells Exocytosis 03 medical and health sciences Mice Catecholamines Cricetulus Cricetinae medicine Animals Protein Isoforms Secretion Research Articles Mice Knockout 030102 biochemistry & molecular biology Monoamine transporter biology Chemistry General Neuroscience Vesicle Calcium-Binding Proteins Cytoplasmic Vesicles Exons Hydrogen-Ion Concentration Cell biology Vesicular monoamine transporter 030104 developmental biology Monoamine neurotransmitter Vesicular Monoamine Transport Proteins biology.protein Catecholamine Female medicine.drug |
| Popis: | The calcium-dependent activator proteins for secretion (CAPS) are priming factors for synaptic and large dense-core vesicles (LDCVs), promoting their entry into and stabilizing the release-ready state. A modulatory role of CAPS in catecholamine loading of vesicles has been suggested. Although an influence of CAPS on monoamine transporter function and on vesicle acidification has been reported, a role of CAPS in vesicle loading is disputed. Using expression of naturally occurring splice variants of CAPS2 into chromaffin cells from CAPS1/CAPS2 double-deficient mice of both sexes, we show that an alternative exon of 40 aa is responsible for enhanced catecholamine loading of LDCVs in mouse chromaffin cells. The presence of this exon leads to increased activity of both vesicular monoamine transporters. Deletion of CAPS does not alter acidification of vesicles. Our results establish a splice-variant-dependent modulatory effect of CAPS on catecholamine content in LDCVs.SIGNIFICANCE STATEMENTThe calcium activator protein for secretion (CAPS) promotes and stabilizes the entry of catecholamine-containing vesicles of the adrenal gland into a release-ready state. Expression of an alternatively spliced exon in CAPS leads to enhanced catecholamine content in chromaffin granules. This exon codes for 40 aa with a high proline content, consistent with an unstructured loop present in the portion of the molecule generally thought to be involved in vesicle priming. CAPS variants containing this exon promote serotonin uptake into Chinese hamster ovary cells expressing either vesicular monoamine transporter. Epigenetic tuning of CAPS variants may allow modulation of endocrine adrenaline and noradrenaline release. This mechanism may extend to monoamine release in central neurons or in the enteric nervous system. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|