Developing protein interactome for rare genetic diseases using BioID technique: Polycystic Kidney Disease and Batten Disease

Candidate: Dhairya Pancholi
Supervisor: Dr. Gagan Gupta

ABSTRACT

Autosomal Dominant Polycystic Kidney Disease is the most common inherited kidney disorder resulting from mutation in either polycystin1 (PC1) or polycystin 2 (PC2) protein. Both proteins interact through their C-terminal coiled-coil tail (CTT) and form a PC complex enriched on the primary cilium. PC1-CTT is particularly interesting as its overexpression or under-expression causes cystic phenotypes. Proximity-dependent Biotin Identification of wildtype PC1-CTT at the primary cilium revealed proteins involved in membrane trafficking, cell junction formation, cell projection, plasma membrane, nucleus, and extracellular region. Alternatively, mutations disrupting PC1-CTT's ability to form PC complex and travel to primary cilium resulted in a loss of several above-mentioned interactors and a gain of some new interactors. Interestingly, all subunits of the BLOC-BORC complex, enriched in the wild-type ciliated data set, were lost in the mutant interactome except for BLOC1S2. Functional analysis of the candidate proteins will provide a better understanding of ADPKD.