Differential regulation of mannose 6-phosphate receptors and their ligands during the myogenic development of C2 cells.
The mammalian insulin-like growth factor II/cation-independent mannose 6-phosphate receptor (IGF-II/CIMPR) mediates both targeting and endocytosis of mannose 6-phosphate-containing proteins and binds insulin-like growth factor II (IGF-II). The cation-dependent mannose 6-phosphate receptor (CDMPR) lacks an IGF-II-binding site and participates only in the intracellular trafficking of lysosomal enzymes. During terminal differentiation of the myogenic C2 cell line, there is an increase in cell surface expression of the IGF-II/CIMPR in parallel with a rise in secretion of IGF-II (Tollefsen, S.E., Sadow, J.L., and Rotwein, P. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 1543-1547). In this study we show that IGF-II/CIMPR mRNA increases by more than 10-fold during the initial 48 h of C2 muscle differentiation with kinetics similar to the rise in IGF-II mRNA. Comparable levels of both mRNAs are expressed in C2 myotubes and in primary cultures of fetal muscle. By contrast, no change is observed in CDMPR transcript abundance during differentiation, and only a small, transient increase is seen in the enzymatic activities and mRNA levels of several lysosomal enzymes. The differential regulation of the two mannose 6-phosphate receptors during muscle differentiation suggests that they may serve distinct functions in development.
Szebenyi
G
G
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Rotwein
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002412:Cations; D002454:Cell Differentiation; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D006863:Hydrogen-Ion Concentration; D006867:Hydrolases / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008024:Ligands; D008247:Lysosomes / Q000201:enzymology; D008360:Mannosephosphates / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009132:Muscles / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D002412:Cations; D008024:Ligands; D008360:Mannosephosphates; D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D011956:Receptors, Cell Surface; D007335:Insulin-Like Growth Factor II; D006867:Hydrolases; D001619:beta-N-Acetylhexosaminidases; D003546:Cysteine Endopeptidases