A. Girod et al., Evidence for a COP-I-independent transport route from the Golgi complex tothe endoplasmic reticulum, NAT CELL BI, 1(7), 1999, pp. 423-430
The cytosolic coat-protein complex COP-I interacts with cytoplasmic 'retrie
val' signals present in membrane proteins that cycle between the endoplasmi
c reticulum (ER) and the Golgi complex, and is required for both anterograd
e and retrograde transport in the secretory pathway, Here we study the role
of COP-I in Golgi-to-ER transport of several distinct marker molecules. Mi
croinjection of anti-COP-I antibodies inhibits retrieval of the lectin-like
molecule ERGIC-53 and of the KDEL receptor from the Golgi to the ER, Trans
port to the ER of protein toxins, which contain a sequence that is recogniz
ed by the KDEL receptor, is also inhibited, In contrast, microinjection of
anti-COP-I antibodies or expression of a GTP-restricted Arf-l mutant does n
ot interfere with Golgi-to-ER transport of Shiga toxin/Shiga-like toxin-1 o
r with the apparent recycling to the ER of Golgi-resident glycosylation enz
ymes. Overexpression of a GDP-restricted mutant of Rab6 blocks transport to
the ER of Shiga toxin/Shiga-like toxin-1 and glycosylation enzymes, but no
t of ERGIC-53, the KDEL receptor or KDEL-containing toxins. These data indi
cate the existence of at least two distinct pathways for Golgi-to-ER transp
ort, one COP-I dependent and the other COP-I independent. The COP-I-indepen
dent pathway is specifically regulated by Rab6 and is used by Golgi glycosy
lation enzymes and Shiga toxin/Shiga-like toxin-1.