Bestrophin-2 antibody

Background of Bestrophin-2 antibody

In the recent past at least 3 different family for “chloride channel” have been characterized: ClC family, ligand gated channels for the GABA and glycine receptor family and the cystic fibrosis membrane conductance regulator. These chloride channels play important role in maintaining resting potentials, ion refluxes, acidification of internal organnles such as lysosomes in both excitatory and non-excitatory nerve and muscle cells. The bestrophins are a newly described family of “anion channels” unrelated in primary sequence to any previously characterized channel proteins. Bestrophins were originally defined as a family of over 20 related sequences of the C. elegans. The first mammalian bestrophin was identified as the vitelliform macular dystrophy (VMD), 1 also known as Best disease (1). Three more members of the bestrophin family members were cloned and identified recently, Bestrophin 2, 3 and 4. The bestrophin family members are membrane protein with 2-TMD and have a conserved 350-400 amino domain including the invariant peptide motif RFP. Each of the Bestrophin proteins has a unique C-terminus that lack similarity to other proteins or motifs. Bestrophin 1 gene is localized to chromosome 19p13.2-p13.12, Bestrophin 2 to 1p32.3-p33 and Bestrophin 3 to 12q14.2-q15. RT-PCR analyses revealed tissue-restricted expression of the three genes with both Bestrophin 1 and Bestrophin 2 are abundantly transcribed in colon. Bestrophin 1 is present in the retinal pigment epithelium while Bestrophin 3 shows predominant expression in skeletal muscle (2, 3). Functionally the Bestrophins oligomerise to form tetramers and pentamers in order to act as calcium sensitive chloride channels. It has been shown that Bestrophin interacts with beta catalytic subunit of protein phosphatase 2A (PP2Ac). Such Protein-protein interaction between bestrophin and PP2Ac and the structural subunit of PP2A, PR65, was confirmed by reciprocal immunoprecipitation. The interaction between PP2Ac and the Bestrophin takes place near the Carboxy-terminal end of the protein. Okadic acid induce the phosphorylation of Bestrophin in vitro. Bestrophin also serves in the signal transduction pathway that modulates the light peak of the EOG, that is regulated by phosphorylation of the Bestrophin that in turn is regulated by protein phosphatase 2A (PP2A).