CHEDIAK-HIGASHI-SYNDROME IS NOT DUE TO A DEFECT IN MICROTUBULE-BASED LYSOSOMAL MOBILITY

Chediak-Higashi Syndrome is an autosomal recessive disorder that affec ts intracellular vesicle formation. The diagnostic feature of Chediak- Higashi Syndrome is the presence of 'giant' lysosomes clustered near t he nucleus. Lysosome morphology in macrophages is maintained by microt ubules and microtubule-based motors, such as kinesin. Dramatic changes in lysosome morphology can be induced by lowering cytoplasmic pH or b y adding phorbol esters. When macrophages from beige mice (a murine ho molog of Chediak-Higashi Syndrome) were subjected to these protocols t hey were able to alter their lysosomal distribution and morphology to the same degree as macrophages from control mice. These results indica te that lysosomes in Chediak cells are capable of interacting with the microtubule-based motor system, suggesting that the defective gene pr oduct is not an altered microtubular element involved in lysosomal mov ement.