Role of endosome-Golgi transport in Batten disease: Btn2 in protein retrieval and inclusion body formation

Btn2 over-production cures yeast from the [URE3] prion (white colonies turn to red), while Btn3 co-expression inhibits curing
Btn2 over-production cures yeast from the [URE3] prion (white colonies turn to red), while Btn3 co-expression inhibits curing

We previously identified BTN2, which is up-regulated upon deletion of the yeast ortholog of the CLN3 Batten disease gene, as encoding a SNARE-binding protein that is connected to endosome-Golgi protein retrieval [Kama et al 2007]. Thus like Btn1, Btn2 and its conserved mammalian Hook orthologs may regulate endosomal protein trafficking to control the Golgi protein localization. We are continuing to study Btn2 functions in endosome-Golgi transport, as well as in the formation of inclusion bodies. Inclusion bodies, such as the IPOD, are localized near late endosomes and are the site of deposition of amyloidogenic and prionogenic proteins when expressed in yeast. Btn2 plays a role in the curing of prions from yeast cells by segregating them away from daughter cells, while a negative regulator of Btn2, called Btn3, enhances the inheritance of the prionic state [Kanneganti et al 2011].
Ongoing work seeks to understand how these proteins regulate inclusion body formation.