Chediak-Higashi syndrome is a genetic disorder caused by mutations in a gene 
encoding a protein named LYST in humans ("lysosomal trafficking regulator") or 
Beige in mice. A prominent feature of this disease is the accumulation of 
enlarged lysosome-related granules in a variety of cells. The genome of 
Dictyostelium discoideum contains six genes encoding proteins that are related 
to LYST/Beige in amino acid sequence, and disruption of one of these genes, lvsA 
(large volume sphere), results in profound defects in cytokinesis. To better 
understand the function of this family of proteins in membrane trafficking, we 
have analyzed mutants disrupted in lvsA, lvsB, lvsC, lvsD, lvsE, and lvsF. Of 
all these, only lvsA and lvsB mutants displayed interesting phenotypes in our 
assays. lvsA-null cells exhibited defects in phagocytosis and contained abnormal 
looking contractile vacuole membranes. Loss of LvsB, the Dictyostelium protein 
most similar to LYST/Beige, resulted in the formation of enlarged vesicles that 
by multiple criteria appeared to be acidic lysosomes. The rates of endocytosis, 
phagocytosis, and fluid phase exocytosis were normal in lvsB-null cells. Also, 
the rates of processing and the efficiency of targeting of lysosomal 
alpha-mannosidase were normal, although lvsB mutants inefficiently retained 
alpha-mannosidase, as well as two other lysosomal cysteine proteinases. Finally, 
results of pulse-chase experiments indicated that an increase in fusion rates 
accounted for the enlarged lysosomes in lvsB-null cells, suggesting that LvsB 
acts as a negative regulator of fusion. Our results support the notion that 
LvsB/LYST/Beige function in a similar manner to regulate lysosome biogenesis.