title: Dynamic maintenance of asymmetric meiotic spindle position through Arp2/3-complex-driven cytoplasmic streaming in mouse oocytes.
abstract: Mature mammalian oocytes are poised for completing meiosis II (MII) on fertilization by positioning the spindle close to an actomyosin-rich cortical cap. Here, we show that the Arp2/3 complex localizes to the cortical cap in a Ran-GTPase-dependent manner and nucleates actin filaments in the cortical cap and a cytoplasmic actin network. Inhibition of Arp2/3 activity leads to rapid dissociation of the spindle from the cortex. Live-cell imaging and spatiotemporal image correlation spectroscopy analysis reveal that actin filaments flow continuously away from the Arp2/3-rich cortex, driving a cytoplasmic streaming expected to exert a net pushing force on the spindle towards the cortex. Arp2/3 inhibition not only diminishes this actin flow and cytoplasmic streaming but also enables a reverse streaming driven by myosin-II-based cortical contraction, moving the spindle away from the cortex. Thus, the asymmetric MII spindle position is dynamically maintained as a result of balanced forces governed by the Arp2/3 complex.
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA.
authors.forename: Kexi
authors.initials: K
authors.lastname: Yi
authors.forename: Jay R
authors.initials: JR
authors.lastname: Unruh
authors.forename: Manqi
authors.initials: M
authors.lastname: Deng
authors.forename: Brian D
authors.initials: BD
authors.lastname: Slaughter
authors.forename: Boris
authors.initials: B
authors.lastname: Rubinstein
authors.forename: Rong
authors.initials: R
authors.lastname: Li
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D051377:Actin-Related Protein 2 / Q000235:genetics / Q000378:metabolism*; D051376:Actin-Related Protein 2-3 Complex / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051378:Actin-Related Protein 3 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003595:Cytoplasmic Streaming / Q000187:drug effects; D005260:Female; D005583:Fourier Analysis; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007734:Kymography; D008540:Meiosis / Q000187:drug effects; D051379:Mice; D018613:Microscopy, Confocal; D018715:Microscopy, Video; D060172:Morpholinos / Q000378:metabolism; D024462:Myosin Type II / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D020931:ran GTP-Binding Protein / Q000378:metabolism
chemical_list: D051377:Actin-Related Protein 2; D051376:Actin-Related Protein 2-3 Complex; D051378:Actin-Related Protein 3; C495927:Actr2 protein, mouse; C495929:Actr3 protein, mouse; C543733:CK-0944666; D006576:Heterocyclic Compounds, 4 or More Rings; D007211:Indoles; D060172:Morpholinos; C102460:Ran protein, mouse; D011993:Recombinant Fusion Proteins; C472645:blebbistatin; D024462:Myosin Type II; D020931:ran GTP-Binding Protein; D015739:Nocodazole