BEST1
BEST1 (bestrophin 1, also known as BMD, BEST, RP50 and VMD2) is a calcium-activated, ligand-gated anion channel of the bestrophin family. It moves chloride and hydrogencarbonate across cell membranes and is linked to inherited macular disease. Browse Assay Genie's current range of BEST1 research reagents below, or read on for the biology behind the target.
BEST1 is a ligand-gated anion channel that allows anions to cross cell membranes when activated by calcium (Ca2+). It permits the movement of chloride and hydrogencarbonate, and is found in a partially open conformation that gives significantly smaller chloride movement. It belongs to the anion channel-forming bestrophin family, in the calcium-sensitive chloride channel subfamily.
In the nervous system, BEST1 acts downstream of receptor signalling in astrocytes. After F2R/PAR-1 activation, calcium released into the cytosol leads to Ca2+-dependent release of L-glutamate into the synaptic cleft, where it targets the neuronal postsynaptic GRIN2A/NMDAR receptor and contributes to the regulation of synaptic plasticity. Following activation of the norepinephrine-alpha-1 adrenergic receptor pathway, BEST1 also transports D-serine as well as L-glutamate in a Ca2+-dependent manner. This activates adjacent NMDA receptors and regulates heterosynaptic long-term depression and metaplasticity during initial memory acquisition. It also releases the neurotransmitter 4-aminobutanoate (GABA) in a Ca2+-dependent manner and takes part in its tonic release from cerebellar glial cells.
The bestrophin family is characterised by a highly conserved N-terminus with four to six transmembrane domains. Bestrophins may form chloride channels or regulate voltage-gated L-type calcium channels. They are generally believed to form calcium-activated chloride channels in epithelial cells, and have been shown to be highly permeable to bicarbonate in retinal tissue. Mutations in the BEST1 gene cause juvenile-onset vitelliform macular dystrophy (VMD2, Best macular dystrophy), adult-onset vitelliform macular dystrophy and other retinopathies, which explains the alias VMD2. Alternative splicing produces multiple distinct isoforms. The mouse ortholog is Best1.
Mutations in the BEST1 gene cause Best macular dystrophy, adult-onset vitelliform macular dystrophy and other retinopathies.
BEST1 is a calcium-activated channel that conducts chloride and hydrogencarbonate, making it a model for bestrophin channel function.
Astrocytic BEST1 releases L-glutamate and D-serine in a Ca2+-dependent manner, activating NMDA receptors and regulating plasticity and memory acquisition.
BEST1 releases 4-aminobutanoate in a Ca2+-dependent manner and participates in tonic release from cerebellar glial cells.
BEST1 is a calcium-activated, ligand-gated anion channel that conducts chloride and hydrogencarbonate across cell membranes. In astrocytes and glia it also mediates Ca2+-dependent release of L-glutamate, D-serine and 4-aminobutanoate, influencing NMDA receptor activity and synaptic plasticity.
BEST1 is the approved symbol for bestrophin 1. Aliases include BMD, BEST, RP50 and VMD2, the last reflecting the previous name vitelliform macular dystrophy 2. Alternative splicing gives multiple distinct isoforms, so check the datasheet of any product for its validated reactivity.
Mutations in the BEST1 gene are responsible for juvenile-onset vitelliform macular dystrophy (Best macular dystrophy), adult-onset vitelliform macular dystrophy and other retinopathies. The protein is highly permeable to bicarbonate in retinal tissue. Mouse has an ortholog, Best1.
Receptors and signalling partners linked to BEST1 function in astrocytes and synaptic regulation.
Gene and protein annotations from HGNC, NCBI Gene and UniProt O76090; product specifications from Assay Genie datasheets.