Plectin scaffolds recruit energy-controlling AMP-activated protein kinase (AMPK) in differentiated myofibres.
Plectin, a cytolinker protein greater than 500 kDa in size, has an important role as a mechanical stabiliser of cells. It interlinks the various cytoskeletal filament systems and anchors intermediate filaments to peripheral junctional complexes. In addition, there is increasing evidence that plectin acts as a scaffolding platform that controls the spatial and temporal localisation and interaction of signaling proteins. In this study we show that, in differentiated mouse myotubes, plectin binds to the regulatory gamma1 subunit of AMP-activated protein kinase (AMPK), the key regulatory enzyme of energy homeostasis. No interaction was observed in undifferentiated myoblasts, and plectin-deficient myotubes showed altered positioning of gamma1-AMPK. In addition we found that plectin affects the subunit composition of AMPK, because isoform alpha1 of the catalytic subunit decreased in proportion to isoform alpha2 during in vitro differentiation of plectin(-/-) myotubes. In plectin-deficient myocytes we could also detect a higher level of activated (Thr172-phosphorylated) AMPK, compared with wild-type cells. Our data suggest a differentiation-dependent association of plectin with AMPK, where plectin selectively stabilises alpha1-gamma1 AMPK complexes by binding to the gamma1 regulatory subunit. The distinct plectin expression patterns in different fibre types combined with its involvement in the regulation of isoform compositions of AMPK complexes could provide a mechanism whereby cytoarchitecture influences energy homeostasis.
Gregor
Martin
M
Department of Molecular Cell Biology, Max F. Perutz Laboratories, University of Vienna, A-1030 Vienna, Austria.
Zeöld
Aniko
A
Oehler
Susanne
S
Marobela
Kerstin Andrä
KA
Fuchs
Peter
P
Weigel
Günter
G
Hardie
D Graham
DG
Wiche
Gerhard
G
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D051190:Plectin / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D051190:Plectin; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D017868:Cyclic AMP-Dependent Protein Kinases