Prof. Anbing SHI and Associate Prof. Long LIN have made innovative progress in the field of polar non-classical secretion and transportation in living cells whose findings have been published in the internationally recognized Journal of Cell Biology (JCB).
It is well-known that unconventional protein secretion (ups) pathways are fairly conservative among species. However, the underlying mechanisms that regulate integral membrane proteins to bypass the Golgi apparatus for UPS transportation remain unclear. In this study, researchers found that RAB-8 and SMGL-1/NBAS are compulsory for the UPS of the integral membrane proteins in the intestine. SMGL-1 is located in that middle compartment of ER-Golgi and the adjacent RAB-8 positive structure, and its subcellular localization requires the NRZ complex component CZW-1/ZW10. Notably, SMGL-1 acts as a guanine nucleotide exchange factor for RAB-8, ensuring integral protein UPS by driving activation of RAB-8. In addition, Pseudomonas aeruginosa infection increases the expression of SMGL-1 and RAB-8. Deletion of SMGL-1 or RAB-8 impairs resistance to environmental colchicine, arsenide and pathogenic bacteria.
These results suggest that SMGL-1/RAB-8-mediated UPS can integrate environmental signals as a host defense response. This study innovatively established the model organism intestine as a multicellular model, on which more frontier research can be carried out, so to provide new in vivo evidence for understanding the regulation mechanism of UPS in living epithelial cells.
The research is supported by the National Key Research and Development Program-Key Special Program, the National Natural Science Foundation of China Key Program, and the National Natural Science Foundation of China Major Research Program. the findings soon received widespread attention from the international academic community and were tweeted 21 times (46,674 followers).
