PDGFRβ and oncogenic mutant PDGFRα D842V promote disassembly of primary cilia through a PLCγ- and AURKA-dependent mechanism.
Primary cilia are microtubule-based sensory organelles projecting from most quiescent mammalian cells, which disassemble in cells cultured in serum-deprived conditions upon re-addition of serum or growth factors. Platelet-derived growth factors (PDGF) are implicated in deciliation, but the specific receptor isoforms and mechanisms involved are unclear. We report that PDGFRβ promotes deciliation in cultured cells and provide evidence implicating PLCγ and intracellular Ca(2+) release in this process. Activation of wild-type PDGFRα alone did not elicit deciliation. However, expression of constitutively active PDGFRα D842V mutant receptor, which potently activates PLCγ (also known as PLCG1), caused significant deciliation, and this phenotype was rescued by inhibiting PDGFRα D842V kinase activity or AURKA. We propose that PDGFRβ and PDGFRα D842V promote deciliation through PLCγ-mediated Ca(2+) release from intracellular stores, causing activation of calmodulin and AURKA-triggered deciliation.
Department of Biology, Section of Cell and Developmental Biology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, Copenhagen OE DK-2100, Denmark.
Brian S
BS
Nielsen
Department of Biology, Section of Cell and Developmental Biology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, Copenhagen OE DK-2100, Denmark.
Raj R
RR
Malinda
Department of Biology, Section of Cell and Developmental Biology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, Copenhagen OE DK-2100, Denmark.
Fabian M
FM
Schmid
Department of Biology, Section of Cell and Developmental Biology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, Copenhagen OE DK-2100, Denmark.
Stine F
SF
Pedersen
Department of Biology, Section of Cell and Developmental Biology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, Copenhagen OE DK-2100, Denmark.
Søren T
ST
Christensen
Department of Biology, Section of Cell and Developmental Biology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, Copenhagen OE DK-2100, Denmark LBPedersen@bio.ku.dk.
Lotte B
LB
Pedersen
D000818:Animals; D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002923:Cilia / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D008856:Microscopy, Fluorescence; D051966:Phospholipase C gamma / Q000378:metabolism*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D064096:Aurora Kinase A; D051966:Phospholipase C gamma
Aurora A kinase; Deciliation; Gastrointestinal stromal tumor; PLCγ; Platelet-derived growth factor receptor; Primary cilia