NCKX disorders

Oculocutaneous albinism (OCA) is a heterogeneous and autosomal recessive hypopigmentation disorder, which is caused by mutations of genes involved in pigment biosynthesis or melanosome biogenesis. We have previously identified NCKX5 (also known as SLC24A5 ) as a causative gene for OCA type 6 (OCA6). However, the pathogenesis of OCA6 is unknown. We found that NCKX5 is localized to mitochondria, not to melanosomes. Pharmacological inhibition of mitochondrial function or NCKX exchanger activity reduced pigment production...

Maintenance of calcium homeostasis is necessary for the development and survival of all animals. Calcium ions modulate excitability and bind effectors capable of initiating many processes such as muscular contraction and neurotransmission. However, excessive amounts of calcium in the cytosol or within intracellular calcium stores can trigger apoptotic pathways in cells that have been implicated in cardiac and neuronal pathologies. Accordingly, it is critical for cells to rapidly and effectively regulate calcium levels...

Control of intracellular calcium signaling is essential for neuronal development and function. Maintenance of Ca2+ homeostasis depends on the functioning of specific transport systems that remove calcium from the cytosol. Na+/Ca2+ exchange is the main calcium export mechanism across the plasma membrane that restores resting levels of calcium in neurons after stimulation. Two families of Na+/Ca2+ exchangers exist, one of which requires the co-transport of K+ and Ca2+ in exchange for Na+ ions. The malfunctioning of Na+/Ca2+ exchangers has been related to the development of pathological conditions in the regulation of neuronal death after hypoxia-anoxia, brain trauma, and nerve injury...