G protein β subunits regulate Ca3.3 T-type channel activity and current kinetics via interaction with the Ca3.3 C-terminus.

Biochim Biophys Acta Biomembr

Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea. Electronic address:

Published: August 2024

Ca influx through Ca3.3 T-type channel plays crucial roles in neuronal excitability and is subject to regulation by various signaling molecules. However, our understanding of the partners of Ca3.3 and the related regulatory pathways remains largely limited. To address this quest, we employed the rat Ca3.3 C-terminus as bait in yeast-two-hybrid screenings of a cDNA library, identifying rat Gβ as an interaction partner. Subsequent assays revealed that the interaction of Gβ subunit was specific to the Ca3.3 C-terminus. Through systematic dissection of the C-terminus, we pinpointed a 22 amino acid sequence (amino acids 1789-1810) as the Gβ interaction site. Coexpression studies of rat Ca3.3 with various Gβγ compositions were conducted in HEK-293 cells. Patch clamp recordings revealed that coexpression of Gβγ reduced Ca3.3 current density and accelerated inactivation kinetics. Interestingly, the effects were not unique to Gβγ but were mimicked by Gβ alone as well as other Gβγ dimers, with similar potencies. Deletion of the Gβ interaction site abolished the effects of Gβγ. Importantly, these Gβ effects were reproduced in human Ca3.3. Overall, our findings provide evidence that Gβ(γ) complexes inhibit Ca3.3 channel activity and accelerate the inactivation kinetics through the Gβ interaction with the Ca3.3 C-terminus.

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http://dx.doi.org/10.1016/j.bbamem.2024.184337DOI Listing

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