Regulation of synthesis of macrophage adhesion molecule, a heterodimeric membrane glycoprotein.
Macrophage adhesion molecule is a surface molecule of guinea pig macrophages and neutrophils. It is the counterpart of mouse Mac-1 and human CD11b/CD18 (Mol/OKM-1/Mac-1/Leu-CAM) and is member of a family of heterodimer glycoproteins with a common beta-subunit. Macrophage adhesion molecule is a prevalent molecule in nonactivated macrophages, but it is dramatically decreased in macrophages activated in vivo. The experimental system of activated vs nonactivated guinea pig peritoneal macrophages was used to examine the mechanisms that down-regulate synthesis of this heterodimer molecule. [35S]Methionine labeling of nonactivated macrophages and chase incubation revealed that synthesis involves separate translation of the alpha- and beta-glycopeptides of "high mannose"-containing monomeric precursors, then refolding/assembly to form a heterodimer, and, finally, a maturation process that includes conversion of carbohydrate to "complex" units. Two lines of evidence demonstrate that down-regulation in activated macrophages occurs via restriction of the alpha-species. First, pre-beta is detected at 3 h only in activated macrophages. Second, the amount of newly translated pre-alpha averaged 16% in activated macrophages relative to nonactivated macrophages, which is close to the value of 12% for the mature heterodimer. The amount of newly translated pre-beta averaged 62%. These findings identify the regulatory step as a restriction of the alpha-species at, or before, translation. A model is proposed to explain regulation of synthesis of heterodimer membrane glycoproteins.
Remold-O'Donnell
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Department of Biological Chemistry, Harvard Medical School, Boston, MA.
D000818:Animals; D005786:Gene Expression Regulation; D006168:Guinea Pigs; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008957:Models, Genetic; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational
D011498:Protein Precursors