1.A.15 The Non-selective Cation Channel-2 (NSCC2) Family
Members of the NSCC2 family have been sequenced from various yeast, fungal and animals species including Saccharomyces cerevisiae, Drosophila melanogaster and Homo sapiens. These proteins are the Sec62 proteins, believed to be associated with the Sec61 and Sec63 constituents of the general protein secretory systems of yeast microsomes. They are also the non-selective cation (NS) channels of the mammalian cytoplasmic membrane. The yeast Sec62 protein has been shown to be essential for cell growth. The mammalian NS channel proteins have been implicated in platelet derived growth factor (PDGF)-dependent single channel current in fibroblasts. These channels are essentially closed in serum deprived tissue-culture cells and are specifically opened by exposure to PDGF. The channels are reported to exhibit equal selectivity for Na+ , K+ and Cs+ with low permeability to Ca2+ , and no permeability to anions. Channel open probability is voltage- and cytoplasmic Ca2+-independent.
Sequenced NSCC2 family proteins are 283-402 amino acyl residues in length and exhibit two putative transmembrane α-helical spanners (TMSs). The S. cerevisiae protein, of 283 amino acyl residues, has cytoplasmic N- and C-termini with two putative TMSs at positions 159-178 and 193-213. The C-terminal 25 residues are rich in arginine and lysine. The animal proteins are about 30% identical to the yeast proteins. It is not known if the yeast proteins can function as ion channels or if the animal proteins facilitate protein secretion. These proteins have been reported to be present in both endoplasmic reticular and cytoplasmic membranes. In spite of their observed low Ca2+ conductance, the mammalian NSCC2 proteins are irreversibly activated by maitotoxin (MTX). MTX may also form pores at higher concentrations (Egido et al., 2008). NSCC2 channels are believed to provide entry pathways in response to growth factors.
The generalized transport reaction catalyzed by members of the NSCC2 family is:
Cation (out) cation (in)