Reaction: BESTs transport cytosolic Cl- to extracellular region
- in pathway: Stimuli-sensing channels
Bestrophins 1-4 (BEST1-4, aka vitelliform macular dystrophy proteins) mediate cytosolic Cl- efflux across plasma membranes. This transport is sensitive to intracellular Ca2+ concentrations (Sun et al. 2002, Tsunenari et al. 2003). Mutations in bestrophins that impair their function are implicated in macular degeneration in the eye. Defects in BEST1 cause vitelliform macular dystrophy (BVMD, Best's disease, MIM:153700), an autosomal dominant form of macular degeneration that usually begins in childhood and is characterized lesions due to abnormal accumulation of lipofuscin within and beneath retinal pigment epithelium (RPE) cells (Marquardt et al. 1998, Petrukhin et al. 1998). All CLCAs contain a consensus cleavage motif which is recognised by an internal zincin metalloprotease domain within the N terminus. Self-proteolysis within the secretory pathway yields N- and C-terminal fragments, a step critical for CLCA activation of calcium-activated chloride channels (CaCCs) mediated through the N-terminal fragment (Yurtsever et al. 2012).
Reaction - small molecule participants:
Cl- [extracellular region]
Cl- [cytosol]
Reactome.org reaction link: R-HSA-2744361
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Reaction input - small molecules:
chloride
Reaction output - small molecules:
chloride
Reactome.org link: R-HSA-2744361