Differential effect of brefeldin A on the palmitoylation of surfactant protein C proprotein mutants.
The surfactant protein C precursor (proSP-C) is palmitoylated on two cysteines adjacent to its transmembrane domain. We showed previously that palmitoylation of proSP-C occurs in a postendoplasmic reticulum compartment and is not affected by the Golgi-disturbing agent brefeldin A (BFA). In contrast, the investigations presented here showed that BFA almost completely abolished palmitoylation of proSP-C mutants that contained alterations in the region between the palmitoylated cysteines and the transmembrane domain, including a Pro 30 to Leu mutant associated with interstitial lung disease. This differential effect of BFA was not caused by differences in the palmitoylation kinetics between wild-type proSP-C and the mutants and was not mimicked by nocodazole and monensin. However, differences between the mutants and wild-type proSP-C in the relative degree of processing suggest that BFA may unmask a difference in routing. This would imply that the amino acids just N-terminal of the transmembrane domain may be important for a proper sorting of proSP-C.
ten Brinke
Anja
A
Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80176, 3508 TD Utrecht, The Netherlands.
Batenburg
Joseph J
JJ
Haagsman
Henk P
HP
van Golde
Lambert M G
LM
Vaandrager
Arie B
AB
D000409:Alanine / Q000737:chemistry; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D020126:Brefeldin A / Q000494:pharmacology*; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D006224:Cricetinae; D003545:Cysteine / Q000737:chemistry; D007150:Immunohistochemistry; D007700:Kinetics; D007930:Leucine / Q000737:chemistry; D009637:Masoprocol / Q000494:pharmacology; D008985:Monensin / Q000494:pharmacology; D009154:Mutation; D015739:Nocodazole / Q000494:pharmacology; D019308:Palmitic Acid / Q000378:metabolism; D010169:Palmitic Acids / Q000378:metabolism*; D010455:Peptides / Q000235:genetics* / Q000378:metabolism*; D011392:Proline / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D000975:Antioxidants; D010169:Palmitic Acids; D010455:Peptides; D011500:Protein Synthesis Inhibitors; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D020126:Brefeldin A; D019308:Palmitic Acid; D009637:Masoprocol; D008985:Monensin; D011392:Proline; D007930:Leucine; D003545:Cysteine; D000409:Alanine; D015739:Nocodazole