Premium
The variant glucose‐6‐phosphate transporter decreases protein stability and requires MyoD‐dependent alternative splicing during myogenesis of muscle cells
Author(s) -
Shieh JengJer,
Chen ChingTung,
Huang WenReu
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a243-b
Subject(s) - myod , myogenesis , c2c12 , alternative splicing , myocyte , myogenin , biology , rna splicing , exon , skeletal muscle , microbiology and biotechnology , biochemistry , endocrinology , gene , rna
The human Glucose‐6‐phosphate transporter (G6PT), glycogen storage disease type 1b defected gene, is expressed ubiquitously, but the G6PT alternative splicing transcript (a variant form of G6PT, vG6PT) is expressed exclusively in the brain, heart, and skeletal muscle. The vG6PT is active in microsomal glucose‐6‐phosphate (G6P) transport, but less effective than G6PT. In this study, we showed the G6PT protein was more stable than vG6PT protein. The exon 7 inclusion in vG6PT may increase the sensitivity for degradation. Although the mouse vG6PT transcripts had the same tissue‐specific alternative splicing pattern as human, the efficiency of alternative splicing in muscle was higher than that in heart and brain tissue. We also showed the vG6PT transcripts were induced during the myogenesis of mouse C2C12 myoblasts. In differentiated myotube, the amount of vG6PT was dramatically increased as compared to undifferentiated myoblast. The down‐regulation of Id1 mRNA after myogenesis beginning, whereas no significant reduction of MyoD mRNA level were correlated to the pattern G6PT alternative splicing during myogenesis. In addition, knock‐down the Id1 expression and exogenous MyoD over‐expression induced the vG6PT alternative splicing in C2C12 myoblasts and in NIH3T3 fibroblasts, respectively. These data suggest that alternative splicing of G6PT can be induced through a common MyoD‐dependent mechanism and may increase the turnover rate of G6PT during myogenesis of muscle cells.