title: CAPS1 effects on intragranular pH and regulation of BDNF release from secretory granules in hippocampal neurons.
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.
authors: Institute of Physiology, Medical Faculty, Otto-von-Guericke-University, Magdeburg 39120, Germany.
authors: Robert
authors: R
authors: Eckenstaler
authors: 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.
authors: Volkmar
authors: V
authors: Lessmann
authors: 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.
authors: Tanja
authors: T
authors: Brigadski
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D022142:Secretory Vesicles / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C510820:Cadps protein, mouse; D002135:Calcium-Binding Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering
keywords: BDNF; CAPS1; Hippocampus; Neuropeptide secretion; Neurotransmitter; Neurotransmitter release; Neurotrophin