Abstract
The AMP-activated protein kinase (AMPK) is an aß? heterotrimer that is activated by low cellular energy status and affects a switch away from energy-requiring processes and toward catabolism [1]. While it is primarily regulated by AMP and ATP, high muscle glycogen has also been shown to repress its activation [2] and [3]. Mutations in the ?2 and ?3 subunit isoforms lead to arrhythmias associated with abnormal glycogen storage in human heart [4], [5], [6] and [7] and elevated glycogen in pig muscle [8], respectively. A putative glycogen binding domain (GBD) has now been identified in the ß subunits. Coexpression of truncated ß subunits lacking the GBD with a and ? subunits yielded complexes that were active and normally regulated. However, coexpression of a and ? with full-length ß caused accumulation of AMPK in large cytoplasmic inclusions that could be counterstained with anti-glycogen or anti-glycogen synthase antibodies. These inclusions were not affected by mutations that increased or abolished the kinase activity and were not observed by using truncated ß subunits lacking the GBD. Our results suggest that the GBD binds glycogen and can lead to abnormal glycogen-containing inclusions when the kinase is overexpressed. These may be related to the abnormal glycogen storage bodies seen in heart disease patients with ?2 mutations.
Original language | English |
---|---|
Pages (from-to) | 861-866 |
Number of pages | 6 |
Journal | Current Biology |
Volume | 13 |
Issue number | 10 |
DOIs | |
Publication status | Published - 2003 |
Keywords
- Cardiac arrhythmias
- Protein kinase
- Glycogen