Here, we investigated a role of one of the putative virulence factors, LmxM.22.0010-encoded BTN1 (a protein involved in Batten disease in humans), in L. mexicana infectivity.
We report that the yeast model for JNCL (btn1-Delta) that lacksBTN1, the homologue to human CLN3, has increased resistance to menadione-generated oxidative stress.
Lymphoblast cell lines established from individuals with juvenile Batten disease (JNCL) bearing mutations in CLN3 and yeast strains lacking Btn1p (btn1-Delta), the homolog to CLN3, have decreased intracellular levels of arginine and defective lysosomal/vacuolar transport of arginine.
The disease severity of Batten disease-causing mutations (G187A, E295K and V330F), when expressed in btn1 appeared to correlate with their effect on vacuolar pH, suggesting that elevated lysosomal pH contributes to the disease process.
We previously reported that deletion of BTN1 (btn1-delta), an ortholog of the human Batten disease gene CLN3, resulted in a decrease in vacuolar pH during early growth.
We propose that up-regulation of Btn2p in btn1-delta is an indicator of altered trafficking within the cell, and as btn1-delta serves as a model for the lysosomal storage disorder Batten disease, that altered intracellular trafficking may contribute to some of the cellular pathological hallmarks of this disease.
Increased expression of HSP30 and BTN2 in btn1-Delta strains and diminished growth of btn1-Delta, hsp30-Delta, and btn2-Delta strains at low pH reinforce our view that altered pH homeostasis is the underlying cause of Batten disease.
BTN1, a yeast gene corresponding to the human gene responsible for Batten's disease, is not essential for viability, mitochondrial function, or degradation of mitochondrial ATP synthase.