Identification and characterization of the single channel function of human mucolipin-1 implicated a disorder affecting the in mucolipidosis type IV, lysosomal pathway

Mucolipin-1 (MLN1) is a membrane protein with homology to the transient receptor potential channels and other non-selective cation channels. It is encoded by the MCOLN1 gene, which is mutated in patients with mucolipidosis type IV (MLIV), an autosomal recessive disease that is characterized by severe abnormalities in neurological development as well as by ophthalmologic defects. At the cellular level, MLIV is associated with abnormal lysosomal sorting and trafficking. Here we identify the channel function of human MLN1 and characterize its properties. MLN1 represents a novel Ca2+-permeable channel that is transiently modulated by changes in [Ca2+]. It is also permeable to Na+ and K+. Large unitary conductances were measured in the presence of these cations. With its Ca2+ permeability and modulation by [Ca2+], MLN1 could play a major role in Ca2+ transport regulating lysosomal exocytosis and potentially other phenomena related to the trafficking of late endosomes and lysosomes. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.