SNX9, SNX18 and SNX33 are required for progression through and completion of mitosis.
Mitosis involves considerable membrane remodelling and vesicular trafficking to generate two independent cells. Consequently, endocytosis and endocytic proteins are required for efficient mitotic progression and completion. Several endocytic proteins also participate in mitosis in an endocytosis-independent manner. Here, we report that the sorting nexin 9 (SNX9) subfamily members - SNX9, SNX18 and SNX33 - are required for progression and completion of mitosis. Depletion of any one of these proteins using siRNA induces multinucleation, an indicator of cytokinesis failure, as well as an accumulation of cytokinetic cells. Time-lapse microscopy on siRNA-treated cells revealed a role for SNX9 subfamily members in progression through the ingression and abscission stages of cytokinesis. Depletion of these three proteins disrupted MRLC(S19) localization during ingression and recruitment of Rab11-positive recycling endosomes to the intracellular bridge between nascent daughter cells. SNX9 depletion also disrupted the localization of Golgi during cytokinesis. Endocytosis of transferrin was blocked during cytokinesis by depletion of the SNX9 subfamily members, suggesting that these proteins participate in cytokinesis in an endocytosis-dependent manner. In contrast, depletion of SNX9 did not block transferrin uptake during metaphase but did delay chromosome alignment and segregation, suggesting that SNX9 plays an additional non-endocytic role at early mitotic stages. We conclude that SNX9 subfamily members are required for mitosis through both endocytosis-dependent and -independent processes.
Children's Medical Research Institute, The University of Sydney, Westmead, NSW 2145, Australia.
Maggie P C
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Megan
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D002462:Cell Membrane / Q000378:metabolism; D020090:Chromosome Segregation; D002877:Chromosomes, Human / Q000378:metabolism; D048749:Cytokinesis; D004705:Endocytosis; D006367:HeLa Cells; D006801:Humans; D007399:Interphase; D008938:Mitosis; D024462:Myosin Type II / Q000378:metabolism; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D058305:Sorting Nexins / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism
D034741:RNA, Small Interfering; C530791:SNX18 protein, human; C531049:SNX33 protein, human; C400533:SNX9 protein, human; D058305:Sorting Nexins; D014168:Transferrin; D024462:Myosin Type II