Journal
JOURNAL OF CELL SCIENCE
Volume 128, Issue 19, Pages 3543-3549Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.173559
Keywords
Aurora A kinase; PLC gamma; Platelet-derived growth factor receptor; Deciliation; Gastrointestinal stromal tumor; Primary cilia
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Funding
- Danish Cancer Society [R56-A3151-12-S2]
- Velux Foundation
- University of Copenhagen Excellence Programme for Interdisciplinary Research
- Government of India
- Department of Biology, University of Copenhagen
- Lundbeck Foundation [R54-2010-5375] Funding Source: researchfish
- Novo Nordisk Fonden [NNF14OC0011535] Funding Source: researchfish
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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 PDGFR beta promotes deciliation in cultured cells and provide evidence implicating PLC gamma and intracellular Ca2+ release in this process. Activation of wild-type PDGFR alpha alone did not elicit deciliation. However, expression of constitutively active PDGFR alpha D842V mutant receptor, which potently activates PLC. (also known as PLCG1), caused significant deciliation, and this phenotype was rescued by inhibiting PDGFR alpha D842V kinase activity or AURKA. We propose that PDGFR beta and PDGFR alpha D842V promote deciliation through PLC gamma-mediated Ca2+ release from intracellular stores, causing activation of calmodulin and AURKA-triggered deciliation.
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