Role of cargo receptors in Synphilin-1 mediated selective autophagy of protein aggregates.
Lee, Karen Feng Yi.
Date of Issue2012
School of Biological Sciences
The ANK-1 domain of synphilin-1 has been recently identified to able to impart autophagic clearance signals to certain disease-linked protein inclusions that were previously resistant to clearance by autophagy. To examine whether ANK1 cooperates with known cargo adaptors, p62 and NBR1, in mediating aggrephagy of ANK1-p38 (A38) inclusions, independent and combinatorial ablation of these cargo adaptors was performed in a wild type and p62 knockout (KO) mouse embryonic fibroblast (MEF) system. By monitoring the turnover and levels of various autophagic markers, we found that variable cargo adaptor levels did not seem to have an impact on the general autophagic function in the cells. Aggrephagic clearance examined by the expression of A38 in p62 KO MEFs to induce inclusion formation demonstrated a significant clearance of protein inclusions that differ only slightly from the clearance presented in wild type cells. Thus, our results revealed that the downregulation of the cargo adaptor protein p62 did not exert a significant impact on synphilin-1 mediated clearance of protein aggregates.
Final Year Project (FYP)
Nanyang Technological University