Mid-Term Report Summary - MUPS (Mechanism of Unconventional Protein Secretion)
2. Based on the current understanding of the unconventional protein secretion, I have proposed a new working hypothesis to explain the pathway used by proteins secreted by this pathway ( Malhotra, V. EMBO J. 2013). I have suggested that the cytoplasmic proteins bind the surface of CUPS, are packed into a new class of carriers that fuse with the endosomes thus delivering the cargoes to the cytoplasmic face of the endosomes. The proteins are then internalized into a small vesicle and the resulting multivesicular body fuses with the plasma membrane to release an exosome like vesicle. The exosome containing the secretory cargo lyses and releases the cargoes into the extracellular space. This mechanism might explain the release of proteins such as interleukin family of cytokines, galectins, tissue transglutaminases and many other cytoplasmic proteins that are secreted in a signal dependent but independent of ER-Golgi pathway of secretion.
The following findings are being assembled for publication and will be submitted in 2014.
1. The biochemical assay for unconventional protein secretion.
2. The mechanism of CUPS formation and disassembly.
3. Purification of CUPS and their biochemical composition.
4. The requirement of GRASP55 in mouse physiology during starvation.