Identification of LMAN1- and SURF4-Dependent Secretory Cargoes

Most proteins secreted into the extracellular space are
first recruited
from the endoplasmic reticulum into coat protein complex II (COPII)-coated
vesicles or tubules that facilitate their transport to the Golgi apparatus.
Although several secreted proteins have been shown to be actively
recruited into COPII vesicles and tubules by the cargo receptors LMAN1
and SURF4, the full cargo repertoire of these receptors is unknown.
We now report mass spectrometry analysis of conditioned media and
cell lysates from HuH7 cells CRISPR targeted to inactivate the LMAN1 or SURF4 gene. We found that LMAN1
has limited clients in HuH7 cells, whereas SURF4 traffics a broad
range of cargoes. Analysis of putative SURF4 cargoes suggests that
cargo recognition is governed by complex mechanisms rather than interaction
with a universal binding motif..