Inversin modulates the cortical actin network during mitosis

Michael E. Werner, Heather H. Ward, Carrie Phillips, Caroline Miller, Vincent H. Gattone, Robert Bacallao

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Mutations in inversin cause nephronophthisis type II, an autosomal recessive form of polycystic kidney disease associated with situs inversus, dilatation, and kidney cyst formation. Since cyst formation may represent a planar polarity defect, we investigated whether inversin plays a role in cell division. In developing nephrons from inv-/- mouse embryos we observed heterogeneity of nuclear size, increased cell membrane perimeters, cells with double cilia, and increased frequency of binuclear cells. Depletion of inversin by siRNA in cultured mammalian cells leads to an increase in bi- or multinucleated cells. While spindle assembly, contractile ring formation, or furrow ingression appears normal in the absence of inversin, mitotic cell rounding and the underlying rearrangement of the cortical actin cytoskeleton are perturbed. We find that inversin loss causes extensive filopodia formation in both interphase and mitotic cells. These cells also fail to round up in metaphase. The resultant spindle positioning defects lead to asymmetric division plane formation and cell division. In a cell motility assay, fibroblasts isolated from inv-/- mouse embryos migrate at half the speed of wild-type fibroblasts. Together these data suggest that inversin is a regulator of cortical actin required for cell rounding and spindle positioning during mitosis. Furthermore, cell division defects resulting from improper spindle position and perturbed actin organization contribute to altered nephron morphogenesis in the absence of inversin.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume305
Issue number1
DOIs
StatePublished - Jul 1 2013

Fingerprint

Mitosis
Actins
Cell Division
Nephrons
Cysts
Embryonic Structures
Autosomal Recessive Polycystic Kidney
Fibroblasts
Cell Migration Assays
Situs Inversus
Pseudopodia
Cilia
Interphase
Metaphase
Actin Cytoskeleton
Morphogenesis
Small Interfering RNA
Dilatation
Cultured Cells
Cell Membrane

Keywords

  • Actin
  • Cytoskeleton
  • Mitosis
  • Mitotic spindle
  • Polycystic kidney disease

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

Inversin modulates the cortical actin network during mitosis. / Werner, Michael E.; Ward, Heather H.; Phillips, Carrie; Miller, Caroline; Gattone, Vincent H.; Bacallao, Robert.

In: American Journal of Physiology - Cell Physiology, Vol. 305, No. 1, 01.07.2013.

Research output: Contribution to journalArticle

Werner, Michael E. ; Ward, Heather H. ; Phillips, Carrie ; Miller, Caroline ; Gattone, Vincent H. ; Bacallao, Robert. / Inversin modulates the cortical actin network during mitosis. In: American Journal of Physiology - Cell Physiology. 2013 ; Vol. 305, No. 1.
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