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J Cell Sci. 2016 Apr 1;129(7):1378-90. doi: 10.1242/jcs.178251. Epub 2016 Feb 11.

CAPS1 effects on intragranular pH and regulation of BDNF release from secretory granules in hippocampal neurons.

Author information

1
Institute of Physiology, Medical Faculty, Otto-von-Guericke-University, Magdeburg 39120, Germany.
2
Institute of Physiology, Medical Faculty, Otto-von-Guericke-University, Magdeburg 39120, Germany Center of Behavioral Brain Sciences (CBBS), Magdeburg 39120, Germany tanja.brigadski@med.ovgu.de volkmar.lessmann@med.ovgu.de.
3
Institute of Physiology, Medical Faculty, Otto-von-Guericke-University, Magdeburg 39120, Germany Center of Behavioral Brain Sciences (CBBS), Magdeburg 39120, Germany tanja.brigadski@med.ovgu.de volkmar.lessmann@med.ovgu.de tanja.brigadski@med.ovgu.de volkmar.lessmann@med.ovgu.de.

Abstract

The secretory protein brain-derived neurotrophic factor (BDNF) is assumed to be a key factor for the induction of synaptic plasticity processes in neurons. However, the molecular mechanisms for activity-dependent release of the protein largely remain elusive. Here, we demonstrate the relevance of the priming factor CAPS1 (also known as CADPS) for the maturation and exocytosis of BDNF-containing secretory granules, as well as for neurotransmitter release from synaptic vesicles. Using live-cell imaging and RNA silencing methods, we show that CAPS1 has a previously unrecognized function in regulating the intragranular pH of BDNF-containing secretory granules. Furthermore, our results demonstrate that acute single-cell knockdown of CAPS1 with unaltered expression in neighboring neurons leads to a strong reduction in the number of fusion-competent secretory granules and to a significant decrease of released BDNF following exocytosis in dendrites of CAPS1-deficient neurons. In addition, our results show a reduction in synaptic vesicle turnover after CAPS1 knockdown without affecting the density of active boutons in hippocampal neurons. Thus, our results reveal new functions of endogenous CAPS1 in the BDNF secretory granule life cycle, thereby representing a new mechanism of neuronal plasticity.

KEYWORDS:

BDNF; CAPS1; Hippocampus; Neuropeptide secretion; Neurotransmitter; Neurotransmitter release; Neurotrophin

PMID:
26869227
DOI:
10.1242/jcs.178251
[Indexed for MEDLINE]
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