PDGFRβ and oncogenic mutant PDGFRα D842V promote disassembly of primary cilia through a PLCγ- and AURKA-dependent mechanism

TY - JOUR

T1 - PDGFRβ and oncogenic mutant PDGFRα D842V promote disassembly of primary cilia through a PLCγ- and AURKA-dependent mechanism

AU - Nielsen, Brian Skriver

AU - Malinda, Raj Rajeshwar

AU - Schmid, Fabian Marc

AU - Pedersen, Stine Helene Falsig

AU - Christensen, Søren Tvorup

AU - Pedersen, Lotte Bang

PY - 2015

Y1 - 2015

N2 - 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 Ca2+ 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 Ca2+ release from intracellular stores, causing activation of calmodulin and AURKA-triggered deciliation.

AB - 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 Ca2+ 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 Ca2+ release from intracellular stores, causing activation of calmodulin and AURKA-triggered deciliation.

U2 - 10.1242/jcs.173559

DO - 10.1242/jcs.173559

M3 - Journal article

C2 - 26290382

SN - 0021-9533

VL - 128

SP - 3543

EP - 3549

JO - Journal of Cell Science

JF - Journal of Cell Science

ER -