Inhibition of secretion by 1,3-cyclohexanebis(methylamine), a dibasic compound that interferes with coatomer function

We noted previously that certain aminoglycoside antibiotics inhibit the bin ding of coatomer to Golgi membranes in vitro. The inhibition is mediated in part by two primary amino groups present at the 1 and 3 positions of the 2 -deoxystreptamine moiety of the antibiotics. These two amines appear to mim ic the epsilon-amino groups present in the two lysine residues of the KKXX motif that is known to bind coatomer. Here we report the effects of 1,3-cyc lohexanebis(methylamine) (CBM) on secretion in vivo, a compound chosen for study because it contains primary amino groups that resemble those in 2-deo xystreptamine and it should penetrate lipid bilayers more readily than anti biotics. CBM inhibited coatomer binding to Golgi membranes in vitro and in vivo and inhibited secretion by intact cells. Despite depressed binding of coatomer in vivo, the Golgi complex retained its characteristic perinuclear location in the presence of CBM and did not fuse with the endoplasmic reti culum (ER). Transport from the ER to the Golgi was also not blocked by CBM. These data suggest that a full complement of coat protein I (COPI) on memb ranes is not critical for maintenance of Golgi integrity or for traffic fro m the ER to the Golgi but is necessary for transport through the Golgi to t he plasma membrane.