How mutations in this gene lead to the disease has been a mystery, but a study led by researchers at Baylor College of Medicine and published in the Journal of Clinical Investigation reveals how defective CLN6 can result in Batten disease.
“People with Batten disease have problems with their cells’ ability to clear cellular waste, which then accumulates to toxic levels,” said first author Dr. Lakshya Bajaj, who was working on this project while a doctorate student in the laboratory of Dr. Marco Sardiello at Baylor.
The Sardiello lab had previously solved a similar mystery involving CLN8, another protein located in the endoplasmic reticulum and whose mutations also cause a type of Batten disease.
When CLN8 is defective, the transport of enzymes from their place of synthesis to the final destination is deficient and the lysosomes end up having fewer enzymes to work with,” said Sardiello, associate professor of molecular and human genetics at Baylor and corresponding author of this work.
Their investigations revealed that CLN6 and CLN8 do interact with each other forming a molecular complex that collects lysosomal enzymes at the endoplasmic reticulum and mediates their trafficking towards the lysosomes.
