AI Article Synopsis

  • GFPT1 is the key enzyme in the hexosamine biosynthetic pathway, with a specific long isoform (GFPT1-L) found in skeletal and cardiac muscles.
  • The regulation of human exon 9 includes proteins like SRSF1 and Rbfox1/2 that enhance inclusion, while hnRNP H/F suppresses it, affecting the recruitment of U1 snRNP.
  • Knockout of GFPT1-L in mice leads to higher levels of GFPT1 and UDP-HexNAc, resulting in impaired glucose uptake, reduced muscle function, and issues with neuromuscular junction stability, suggesting GFPT1-L plays a crucial role in energy production and muscle health in mammals.

Article Abstract

Glutamine:fructose-6-phosphate transaminase 1 (GFPT1) is the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP). A 54-bp exon 9 of is specifically included in skeletal and cardiac muscles to generate a long isoform of GFPT1 (GFPT1-L). We showed that SRSF1 and Rbfox1/2 cooperatively enhance, and hnRNP H/F suppresses, the inclusion of human exon 9 by modulating recruitment of U1 snRNP. Knockout (KO) of GFPT1-L in skeletal muscle markedly increased the amounts of GFPT1 and UDP-HexNAc, which subsequently suppressed the glycolytic pathway. Aged KO mice showed impaired insulin-mediated glucose uptake, as well as muscle weakness and fatigue likely due to abnormal formation and maintenance of the neuromuscular junction. Taken together, GFPT1-L is likely to be acquired in evolution in mammalian striated muscles to attenuate the HBP for efficient glycolytic energy production, insulin-mediated glucose uptake, and the formation and maintenance of the neuromuscular junction.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514471PMC
http://dx.doi.org/10.1016/j.isci.2023.107746DOI Listing

Publication Analysis

Top Keywords

neuromuscular junction
12
insulin-mediated glucose
8
glucose uptake
8
formation maintenance
8
maintenance neuromuscular
8
splicing regulation
4
gfpt1
4
regulation gfpt1
4
gfpt1 muscle-specific
4
muscle-specific isoform
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!