Association of phosphofructokinase-M with caveolin-3 in differentiated skeletal myotubes: Dynamic regulation by extracellular glucose and intracellular metabolites

Philipp E. Scherer, Michael P. Lisanti

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Caveolin-3 is a member of the caveolin family of proteins that is primarily expressed in striated muscle cell types (skeletal and cardiac). Here, we show that an ~80-kDa protein specifically co-immunoprecipitates with caveolin-3 expressed in differentiated skeletal C2C12 myotubes. Microsequence analysis of this ~80-kDa polypeptide revealed its identity as a key regulatory enzyme in the glycolytic pathway, namely phosphofructokinase-M (PFK-M). Pulse-chase experiments demonstrate that PFK- M associates with caveolin-3 with a significant time lag after the biosynthesis of PFK-M. In addition, we show that this interaction is (i) highly regulated by the extracellular concentration of glucose and (ii) can be stabilized by a number of relevant intracellular metabolites, such as fructose 1,6-bisphosphate and fructose 2,6-bisphosphate, which are known allosteric activators of PFK. While the bulk of these experiments were performed in C2C12 cells, identical results were obtained using mouse skeletal muscle extracts. Taken together, our results suggest that glucose- dependent plasma membrane recruitment of activated PFK-M by caveolin-3 could have important implications for understanding the mechanisms that regulate energy metabolism in skeletal muscle fibers.

Original languageEnglish (US)
Pages (from-to)20698-20705
Number of pages8
JournalJournal of Biological Chemistry
Volume272
Issue number33
DOIs
StatePublished - Aug 15 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Association of phosphofructokinase-M with caveolin-3 in differentiated skeletal myotubes: Dynamic regulation by extracellular glucose and intracellular metabolites'. Together they form a unique fingerprint.

  • Cite this