Syndecan-4 promotes cytokinesis in a phosphorylation-dependent manner.
During mitosis, cells detach, and the cell-matrix interactions become restricted. At the completion of cytokinesis, the two daughter cells are still connected transiently by an intercellular bridge (ICB), which is subjected to abscission, as the terminal step of cytokinesis. Cell adhesion to the matrix is mediated by syndecan-4 (SDC4) transmembrane heparan sulfate proteoglycan. Our present work demonstrated that SDC4 promotes cytokinesis in a phosphorylation-dependent manner in MCF-7 breast adenocarcinoma cells. The serine179-phosphorylation and the ectodomain shedding of SDC4 changed periodically in a cell cycle-dependent way reaching the maximum at G2/M phases. On the contrary, the phospho-resistant Ser179Ala mutant abrogated the shedding. The phosphorylated full-length and shed remnants enriched along the mitotic spindles, and subsequently in the ICBs, however, proper membrane insertion was necessary for midbody localization. Expression of phosphomimicking Ser179Glu SDC4 resulted in incomplete abscission, whereas expression of the phospho-resistant SDC4 led to giant, multinucleated cells.
2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
Aniko
A
Keller-Pinter
Sandor
S
Bottka
Jozsef
J
Timar
Janina
J
Kulka
Robert
R
Katona
Laszlo
L
Dux
Ferenc
F
Deak
Laszlo
L
Szilak
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019943:Amino Acid Substitution; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D048749:Cytokinesis / Q000502:physiology*; D005260:Female; D015726:Giant Cells / Q000378:metabolism / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008856:Microscopy, Fluorescence; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D008941:Spindle Apparatus / Q000378:metabolism; D053671:Syndecan-4 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D011993:Recombinant Fusion Proteins; C508304:SDC4 protein, human; D053671:Syndecan-4; D049452:Green Fluorescent Proteins; D012694:Serine