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 binding 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 mimic 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-cyclohexanebis(methylamine) (CBM) on secretion in vivo, a compound chosen for study because it contains primary amino groups that resemble those in 2-deoxystreptamine and it should penetrate lipid bilayers more readily than antibiotics. 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 reticulum (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 membranes is not critical for maintenance of Golgi integrity or for traffic from the ER to the Golgi but is necessary for transport through the Golgi to the plasma membrane.
Hu
T
T
The Molecular and Cell Biology Department, The University of Texas at Dallas, Richardson, Texas 75083-0688, USA.
Kao
C Y
CY
Hudson
R T
RT
Chen
A
A
Draper
R K
RK
D033982:Adaptor Protein Complex gamma Subunits; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D016466:CHO Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D020756:Coatomer Protein; D006224:Cricetinae; D003510:Cyclohexanes / Q000737:chemistry / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism; D006595:Hexosamines / Q000737:chemistry / Q000494:pharmacology; D007668:Kidney; D008361:Mannosidases / Q000378:metabolism; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D008744:Methylamines / Q000737:chemistry / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014162:Transfection
D033982:Adaptor Protein Complex gamma Subunits; D000900:Anti-Bacterial Agents; D020756:Coatomer Protein; D003510:Cyclohexanes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006595:Hexosamines; D008565:Membrane Proteins; D008744:Methylamines; D011500:Protein Synthesis Inhibitors; C118804:1,3-cyclohexanebis(methylamine); D008361:Mannosidases; C038829:mannosyl-oligosaccharide 1,3 - 1,6-alpha-mannosidase; D019204:GTP-Binding Proteins; C007265:2-deoxystreptamine