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

FEBS Letters

Vassilev, Peter M³  Kanazirska, Marie³  Brown, Edward M³  LaPlante, Janice M³  Sun, Mei¹  Falardeau, John²  Slaugenhaupt, Susan A² 

[1]Center for Prostate Disease Research, Rockville, MD 20852, USA

[2]Molecular Neurogenetics Unit, Massachusetts General Hospital and Harvard Institute of Human Genetics, Harvard Medical School, Boston, MA 02115, USA

[3]Division of Endocrinology, Diabetes and Hypertension and Membrane Biology Program, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., Boston, MA 02115, USA

关键词: Mucolipin;    Mucolipidosis;    Lysosome;    Exocytosis;    Channel;    Late endosome;   

DOI  :  10.1016/S0014-5793(02)03670-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown