Role of cargo receptors in Synphilin-1 mediated selective autophagy of protein aggregates.
Tan, Charlene Yan Ning.
Date of Issue2012
School of Biological Sciences
Aggrephagy is a macroautophagy pathway that selectively degrades protein aggregates. Cargo adaptor proteins, NBR1 and p62, have been found to selectively sequester protein aggregates into autophagosome for lysosomal degradation via autophagic pathway. Moreover, the Sphilin-1 protein contains an ANK1 domain that enables it to promote aggrephagy of autophagy non-amendable protein aggregates. However, the basic molecular mechanism behind this degradative pathway is still unknown. Since both Sphilin-1 and cargo adaptors share similar functions in aggrephagy, this study was done to determine if cargo receptors play a role in Sphilin-1 mediated aggrephagy in p62 and NBR1 knockdown cells. Furthermore, additional experiments were conducted in p62 and NBR1 deficient cells to determine their effect on selective autophagy. Results show that p62 and NBR1 may not be necessary for selective autophagy. Sph-1 mediated clearance of protein aggregates was discovered to be independent of p62 cargo adaptor protein. Together, these findings helps to unravel the mechanistic function of cargo receptors and their role in selective autophagy, be it starvation-induced or Sph-1 mediated.
Final Year Project (FYP)
Nanyang Technological University