title: TrkAIII promotes microtubule nucleation and assembly at the centrosome in SH-SY5Y neuroblastoma cells, contributing to an undifferentiated anaplastic phenotype.
abstract: The alternative TrkAIII splice variant is expressed by advanced stage human neuroblastomas (NBs) and exhibits oncogenic activity in NB models. In the present study, employing stable transfected cell lines and assays of indirect immunofluorescence, immunoprecipitation, Western blotting, microtubule regrowth, tubulin kinase, and tubulin polymerisation, we report that TrkAIII binds α -tubulin and promotes MT nucleation and assembly at the centrosome. This effect depends upon spontaneous TrkAIII activity, TrkAIII localisation to the centrosome and pericentrosomal area, and the capacity of TrkAIII to bind, phosphorylate, and polymerise tubulin. We propose that this novel role for TrkAIII contributes to MT involvement in the promotion and maintenance of an undifferentiated anaplastic NB cell morphology by restricting and augmenting MT nucleation and assembly at the centrosomal MTOC.
authors.affiliation: Department of Applied Clinical and Biotechnological Sciences, University of L'Aquila, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy.
authors.forename: Antonietta R
authors.initials: AR
authors.lastname: Farina
authors.forename: Natalia
authors.initials: N
authors.lastname: Di Ianni
authors.forename: Lucia
authors.initials: L
authors.lastname: Cappabianca
authors.forename: Pierdomenico
authors.initials: P
authors.lastname: Ruggeri
authors.forename: Marzia
authors.initials: M
authors.lastname: Ragone
authors.forename: Giulia
authors.initials: G
authors.lastname: Ianni
authors.forename: Alberto
authors.initials: A
authors.lastname: Gulino
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Mackay
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D045744:Cell Line, Tumor; D018385:Centrosome / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008870:Microtubules / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation; D011485:Protein Binding; D020917:Receptor, trkA / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014404:Tubulin / Q000378:metabolism*
chemical_list: D014404:Tubulin; D020917:Receptor, trkA