BACKGROUND: Chediak-Higashi syndrome (CHS) is an inherited immunodeficiency 
disease characterized by giant lysosomes and impaired leukocyte degranulation. 
CHS results from mutations in the lysosomal trafficking regulator (LYST) gene, 
which encodes a 425-kD cytoplasmic protein of unknown function. The goal of this 
study was to identify proteins that interact with LYST as a first step in 
understanding how LYST modulates lysosomal exocytosis.
MATERIALS AND METHODS: Fourteen cDNA fragments, covering the entire coding 
domain of LYST, were used as baits to screen five human cDNA libraries by a 
yeast two-hybrid method, modified to allow screening in the activation and the 
binding domain, three selectable markers, and more stringent confirmation 
procedures. Five of the interactions were confirmed by an in vitro binding 
assay.
RESULTS: Twenty-one proteins that interact with LYST were identified in yeast 
two-hybrid screens. Four interactions, confirmed directly, were with proteins 
important in vesicular transport and signal transduction (the SNARE-complex 
protein HRS, 14-3-3, and casein kinase II).
CONCLUSIONS: On the basis of protein interactions, LYST appears to function as 
an adapter protein that may juxtapose proteins that mediate intracellular 
membrane fusion reactions. The pathologic manifestations observed in CHS 
patients and in mice with the homologous mutation beige suggest that 
understanding the role of LYST may be relevant to the treatment of not only CHS 
but also of diseases such as asthma, urticaria, and lupus, as well as to the 
molecular dissection of the CHS-associated cancer predisposition.