RTG-ReMPro
Projects
P5 Baukrowitz
Regulation of THIK-1 K+ homo- and heterodimeric channels
by proteolytic processing and membrane phosphoinositides
Objectives
We propose to characterize the posttranslational reversible phosphoinositide and irreversible caspase-8 regulation of THIK-1 channels in electrophysiological experiments. To uncover the structural mechanisms of this regulation we will explore THIK-1 channels with gradually truncated C-termini. The impact of their heterodimerization with TWIK-1 and TWIK-2 subunits on channel activity and localization will be investigated, as well as the physiological relevance in macrophages and microglia.
Aim i) The doctoral researchers of the first period will conduct additional experiments on the reversible PIP2-induced regulation of THIK-1 channels
Aim ii) In the second period the heteromerization of THIK-1 and TWIK- channels will be explored
K2P channels play a pivotal role in microglial physiology. THIK-1 channels are essential for ramified microglia surveilling the neuronal integrity. They are activated by PIP2 that is formatted after microglia activation and are involved in caspase-8 induced apoptosis. Members of two K2P subunits are involved in NLRP3 inflammasome activation. The influence of heteromer formation of the channels in this process is completely unknown.
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