Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Traffic - International Journal of Intracellular Transport |
| ISSN | 1398-9219 |
| DOI | |
| Status | Udgivet - 2010 |
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I: Traffic - International Journal of Intracellular Transport, 2010.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Rab3 proteins involved in vesicle biogenesis and priming in embryonic mouse chromaffin cells
AU - Schonn, Jean-Sébastien
AU - van Weering, Jan R T
AU - Mohrmann, Ralf
AU - Schlüter, Oliver M
AU - Südhof, Thomas C
AU - de Wit, Heidi
AU - Verhage, Matthijs
AU - Sørensen, Jakob B
PY - 2010
Y1 - 2010
N2 - The four Rab3 paralogs A-D are involved in exocytosis, but their mechanisms of action are hard to study due to functional redundancy. Here we used a quadruple Rab3 knock-out (rab3a, rab3b, rab3c, rab3d null, here denoted ABCD(-/-)) mouse line to investigate Rab3 function in embryonic mouse adrenal chromaffin cells by electron microscopy and electrophysiological measurements. We show that in cells from ABCD(-/-) animals large dense core vesicles (LDCVs) are less abundant while the number of morphologically docked granules is normal. By capacitance measurements, we show that deletion of Rab3s reduces the size of the releasable vesicle pools but does not alter their fusion kinetics, consistent with an altered function in vesicle priming. The sustained release component has a sigmoid shape in ABCD(-/-) cells when normalized to the releasable pool size, indicating that vesicle priming follows at a higher rate after an initial delay. Rescue experiments showed that short-term (4-6 hours) overexpression of Rab3A or Rab3C suffices to rescue vesicle priming and secretion, but it does not restore the number of secretory vesicles. We conclude that Rab3 proteins play two distinct stimulating roles for LDCV fusion in embryonic chromaffin cells, by facilitating vesicle biogenesis and stabilizing the primed vesicle state.
AB - The four Rab3 paralogs A-D are involved in exocytosis, but their mechanisms of action are hard to study due to functional redundancy. Here we used a quadruple Rab3 knock-out (rab3a, rab3b, rab3c, rab3d null, here denoted ABCD(-/-)) mouse line to investigate Rab3 function in embryonic mouse adrenal chromaffin cells by electron microscopy and electrophysiological measurements. We show that in cells from ABCD(-/-) animals large dense core vesicles (LDCVs) are less abundant while the number of morphologically docked granules is normal. By capacitance measurements, we show that deletion of Rab3s reduces the size of the releasable vesicle pools but does not alter their fusion kinetics, consistent with an altered function in vesicle priming. The sustained release component has a sigmoid shape in ABCD(-/-) cells when normalized to the releasable pool size, indicating that vesicle priming follows at a higher rate after an initial delay. Rescue experiments showed that short-term (4-6 hours) overexpression of Rab3A or Rab3C suffices to rescue vesicle priming and secretion, but it does not restore the number of secretory vesicles. We conclude that Rab3 proteins play two distinct stimulating roles for LDCV fusion in embryonic chromaffin cells, by facilitating vesicle biogenesis and stabilizing the primed vesicle state.
U2 - 10.1111/j.1600-0854.2010.01107.x
DO - 10.1111/j.1600-0854.2010.01107.x
M3 - Journal article
C2 - 20716109
SN - 1398-9219
JO - Traffic - International Journal of Intracellular Transport
JF - Traffic - International Journal of Intracellular Transport
ER -