Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA274

Poster Communications

The paralogs of the calcium-dependent activator protein for secretion differentially regulate synaptic transmission and peptide secretion in murine dorsal root ganglion neurons

A. Shaib1,2, A. Staudt1, A. Harb1, M. Klose1, A. Shaaban1, C. Schirra1, R. Mohrmann1,3, J. Rettig1, U. Becherer1

1. Institute of Physiology, CIPMM, Saarland University, Homburg, Germany. 2. Department of Molecular Neurobiology, MPI for experimental medicine, Göttingen, Germany. 3. Institute of Physiology, Otto-von-Guericke University, Magdeburg, Germany.

The two paralogs of the calcium-dependent activator protein for secretion (CAPS) are priming factors for synaptic vesicles and neuropeptide containing large dense-core vesicles (LDCVs). Yet, it is unclear whether CAPS1 and CAPS2 regulate exocytosis of these two vesicles types differentially in systems such as dorsal root ganglion (DRG) neurons, where synaptic transmission and neuropeptide release are of equal importance. These sensory neurons transfer information from the periphery to the spinal cord, releasing glutamate as the primary neurotransmitter, with co-transmission via neuropeptides in a subset of so called peptidergic neurons. Neuropeptides are key components of the information-processing machinery of pain perception and neuropathic pain generation. Here, we compared the ability of CAPS1 and CAPS2 to support priming of both vesicle types in single and double knock-out mouse (DRG) neurons using a variety of high-resolution live imaging methods. While CAPS1 was localized to synapses of all DRG neurons and promoted synaptic transmission, CAPS2 was found exclusively in peptidergic neurons and mediated LDCV exocytosis. Intriguingly, ectopic expression of CAPS2 empowered non-peptidergic neurons to drive LDCV fusion, thereby identifying CAPS2 as an essential molecular determinant for peptidergic signaling. Our results reveal that these distinct functions of both CAPS paralogs are based on their differential subcellular localization in DRG neurons. Our data imply a major role for CAPS2 in neuropathic pain via control of neuropeptide release.

Where applicable, experiments conform with Society ethical requirements