TRPC3 Membrane Protein Introduction

Introduction of TRPC3

Short transient receptor potential channel 3 (TRPC3), encoded by the TRPC3 gene, is one of the classical members of the mammalian transient receptor potential (TRP) superfamily of ion channels. TRPC3 is a non-specific ion channel permeable to calcium and many other cations. Similar to other TRPC channels, TRPC3 features six transmembrane spanning segments with nitrogen (N) and carbon (C) termini residing in the cytoplasm. TRPC3 assembles into tetrameric complexes, which form a cation permeation path with a selectivity filter harboring negatively charged residues to determine calcium ion (Ca²⁺) transport within the pore domains, connecting transmembrane domains 5 and 6 (TM5 and TM6).

Function of TRPC3 Membrane Protein

TRPC3 is ubiquitously expressed in the cerebellum, cerebrum, and smooth muscles, where it appears to control functions of the cardiovascular system and the brain in a highly specific manner. Especially, TRPC3 plays essential roles in the regulation of neurogenesis and extracellular/intracellular calcium signaling. Dysfunction of TRPC3 has been linked to neurodegenerative disease, cardiac hypertrophy, and ovarian adenocarcinoma. Moreover, it has been reported that TRPC3 plays a role in immunity, cancer, and tissue remodeling, generating much interest in TRPC3 as a target for pharmacological intervention. In basal ganglia (BG) output neurons, TRPC3 channels are involved in maintaining a tonic inward depolarizing current that promotes regular neuronal firing and regulates resting membrane potential. On the contrary, inhibiting TRPC3 will facilitate cellular hyperpolarization, which can result in more irregular and slower neuronal firing. TRPC3 can be activated by neuromodulator diacylglycerols (DAG) and substance P.

Fig.1 Cryo-EM structure of human TRPC3 at 4.36A resolution. (Tang, 2018)

Application of TRPC3 Membrane Protein in Literature

1. Tian J. and Zhu M.X. Gq activity-and β-arrestin-1 scaffolding-mediated TRPC3/CFTR coupling are required for male fertility. Cells. 2018, 7(8). pii: E90. PubMed ID: 30060610
   
   

   This article concludes that postsynaptic GABABRs modulate Purkinje cell responses to strong glutamatergic stimulation through regulation of mGluR1-TRPC3 coupling.

2. Tang Q., et al. Structure of the receptor-activated human TRPC6 and TRPC3 ion channels. Cell Res. 2018, 28(7):746-755. PubMed ID: 29700422
   
   

   This article determines the structure of human TRPC3 by single-particle cryo-electron microscopy to 4.4 Å resolution.

3. Xu B.M., et al. TRPC3 overexpression and intervention in airway smooth muscle of ovalbumin-induced hyperresponsiveness and remodeling. Cell Biol Int. 2018, 42(8):1021-1029. PubMed ID: 29624776
   
   

   This article confirms that overexpression of TRPC3 protein may be associated with hyperresponsiveness of airway smooth muscle and remodeling in asthmatic mice, providing evidence for a new target for drug intervention and a new direction of asthma pathogenesis research.

4. Lichtenegger M., et al. An optically controlled probe identifies lipid-gating fenestrations within the TRPC3 channel. Nat Chem Biol. 2018, 14(4):396-404. PubMed ID: 29556099
   
   

   This report provides evidence for a novel concept of lipid-sensing by TRPC ion channels based on a lateral fenestration in the pore domain which accommodates lipid mediators to control gating.

5. Hao H.B., et al. TRPC3 is required for the survival, pluripotency and neural differentiation of mouse embryonic stem cells (mESCs). Sci China Life Sci. 2018, 61(3):253-265. PubMed ID: 29392682
   
   

   This article demonstrates an important role of TRPC3 with regards to the pluripotency, survival and neural differentiation of mouse embryonic stem cells.

TRPC3 Preparation Options

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Reference

1. Tang Q, et al. (2018). Structure of the receptor-activated human TRPC6 and TRPC3 ion channels. Cell Res. 28: 746-755.

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