DAAD/SAV

Novel interaction partners of the CaV2.2 channel        

Vedúca projektu: Ľubica Lacinová

Trvanie: jún 2016 – január 2017
Koordinujúca organizácia: Centrum biovied – Ústav molekulárnej fyziológie a genetiky SAV, Bratislava

Anotácia:

Neurotransmission controlled by CaV2.2 or N-type calcium channels plays a major role in chronic and neuropathic pain which is a major clinical, social and economic problem. Ziconotide is the only one drug specifically targeting CaV2.2 channel. It is delivered intrathecally leaving demand for an oral drug open. Ion channels form macromolecular signaling complexes with a variety of interacting proteins and stabilization or disruption of such interactions may be a base for a novel therapeutic strategy. Modified yeast-two-hybrid assay identified proteins RTN1, SLC38A1, Ptgds, TMEM 223, and Grina as putative interaction partners of the CaV2.2 channels. These proteins are expressed predominantly or solely in neurons and several neuromodulatory functions of these proteins were described. We hypothesize that they may modulate CaV2.2 channels, as well.

Kľúčové slová:

CaV2.2 channel, neuropathic pain, patch clamp, co-immunoprecipitation

Ciele:

We will concentrate on following aspect of the CaV2.2 channel interactome:

1. Regulation of voltage- and time-dependent activity of the CaV2.2 channel itself. Main role of CaV2.2 channels is generation of large but temporally precise calcium influx into presynaptic neurons. Even minor change in the channel gating may translate into significant modulation of synaptic transmission.

2. Modulation of a downstream regulatory pathways. We will investigate modulation of CaV2.2 channels activity by intracellular messengers and/or G-proteins in the absence or presence of each interacting protein.

3. Co-immunoprecipitation studies as well as immunocytochemistry studies confirming colocalization and interaction of the CaV2.2 protein with putative interaction partners.