title: SEPT9_v4 expression induces morphological change, increased motility and disturbed polarity.
abstract: Several lines of evidence indicate that altered expression of SEPT9 is seen in human neoplasia. In particular there is evidence of altered expression of the SEPT9_v4 isoform. The functional consequences of this remain unclear. We have studied the expression of wild-type- and GTP-binding mutants (G144V and S148N) of the SEPT9_v4 isoform in the MCF7 cell line as a model for its deregulation in neoplasia. We find that SEPT9_v4 expression induces dramatic actin cytoskeletal reorganization with the formation of processes around the cell periphery. Expression of the SEPT9_v4 isoform and a G144V mutant cause delocalization of endogenous SEPT9 from filamentous structures but the S148N mutant does not have this effect. In addition SEPT9_v4 isoform expression enhances cell motility and is associated with perturbation of directional movement. Expression of SEPT9_v4 GTP binding mutants also has potent effects on morphology and motility and causes loss of normal polarity, as judged by Golgi reorientation assays. The phenotypes induced by expression of the SEPT9_v4 isoform and the GTP mutants provide an insight into possible mechanisms of SEPT9_v4 function and suggest that the GTPase functions have both ras- and rab-like features. We propose a model in which overexpression of the SEPT9_v4 isoform in neoplasia is associated with perturbation of SEPT9 complexes, leading to phenotypes associated with neoplasia.
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University Belfast, U Floor, City Hospital, Lisburn Road, Belfast BT9 7AB, UK.
authors.forename: Alex D
authors.initials: AD
authors.lastname: Chacko
authors.forename: Paula L
authors.initials: PL
authors.lastname: Hyland
authors.forename: Simon S
authors.initials: SS
authors.lastname: McDade
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hamilton
authors.forename: Se Hilary
authors.initials: SH
authors.lastname: Russell
authors.forename: Peter A
authors.initials: PA
authors.lastname: Hall
mesh_terms: D000199:Actins / Q000032:analysis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D003599:Cytoskeleton / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006056:Golgi Apparatus / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics; D058112:Septins; D019076:Transgenes / Q000235:genetics
chemical_list: D000199:Actins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D020558:GTP Phosphohydrolases; C474315:SEPTIN9 protein, human; D058112:Septins