Targeting of dystroglycan to the cleavage furrow and midbody in cytokinesis.
Dystroglycan is a cell adhesion molecule that interacts with ezrin family proteins and also components of the extracellular signal-regulated kinase pathway. Ezrin and extracellular signal-regulated kinase are both involved in aspects of the cell division cycle. We therefore examined the role of dystroglycan during cytokinesis. Endogenous dystroglycan colocalised with ezrin at the cleavage furrow and midbody during cytokinesis in REF52 cells. Live cell imaging of green fluorescent protein-tagged dystroglycan in Swiss 3T3 and Hela cells revealed a similar localisation. Live cell imaging of a dystroglycan lacking its cytoplasmic domain revealed an even membrane localisation but no cleavage furrow or midbody localisation. Deletion of a previously identified ezrin-binding site in the dystroglycan cytoplasmic domain however only resulted in a slight reduction in cleavage furrow localisation but loss of midbody staining. There was no apparent cytokinetic defect in cells depleted for dystroglycan, however apoptosis levels were considerably higher in dystroglycan knockdown cells. Cell cycle analysis showed a delay in G2/M transition, possibly caused by a more than 50% reduction in extracellular signal-regulated kinase levels in the knockdown cells. Dystroglycan may therefore not only have a role in organising the contractile ring through direct or indirect associations with actin, but can also modulate the cell cycle by affecting extracellular signal-regulated kinase levels.
Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
J R
JR
Higginson
O
O
Thompson
S J
SJ
Winder
D008841:Actin Cytoskeleton / Q000737:chemistry; D000818:Animals; D002453:Cell Cycle; D048749:Cytokinesis; D049030:Dystroglycans / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D017434:Protein Structure, Tertiary; D041701:Swiss 3T3 Cells
D049030:Dystroglycans; D048049:Extracellular Signal-Regulated MAP Kinases