RRC ID 76322
Author Wang X, Li X, Wang J, Wang J, Hu C, Zeng J, Shi A, Lin L.
Title SMGL-1/NBAS acts as a RAB-8 GEF to regulate unconventional protein secretion.
Journal J Cell Biol
Abstract Unconventional protein secretion (UPS) pathways are conserved across species. However, the underlying mechanisms that regulate Golgi-bypassing UPS of integral proteins remain elusive. In this study, we show that RAB-8 and SMGL-1/NBAS are required for the UPS of integral proteins in C. elegans intestine. SMGL-1 resides in the ER-Golgi intermediate compartment and adjacent RAB-8-positive structures, and NRZ complex component CZW-1/ZW10 is required for this residency. Notably, SMGL-1 acts as a guanine nucleotide exchange factor for RAB-8, ensuring UPS of integral proteins by driving the activation of RAB-8. Furthermore, we show that Pseudomonas aeruginosa infection elevated the expression of SMGL-1 and RAB-8. Loss of SMGL-1 or RAB-8 compromised resistance to environmental colchicine, arsenite, and pathogenic bacteria. These results suggest that the SMGL-1/RAB-8-mediated UPS could integrate environmental signals to serve as a host defense response. Together, by establishing the C. elegans intestine as a multicellular model, our findings provide insights into RAB-8-dependent Golgi-bypassing UPS, especially in the context of epithelia in vivo.
Volume 221(7)
Published 2022-7-4
DOI 10.1083/jcb.202111125
PII 213235
PMID 35604368
PMC PMC9129922
MeSH Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Golgi Apparatus / metabolism Guanine Nucleotide Exchange Factors* / genetics Guanine Nucleotide Exchange Factors* / metabolism Protein Transport rab GTP-Binding Proteins* / genetics rab GTP-Binding Proteins* / metabolism
C.elegans tm2526 tm2518 tm1447