Rab23/Kif17 regulate meiotic progression in oocytes by modulating tubulin acetylation and actin dynamics

Development. 2019 Feb 4;146(3):dev171280. doi: 10.1242/dev.171280.

Abstract

Cytoskeletal dynamics are involved in multiple cellular processes during oocyte meiosis, including spindle organization, actin-based spindle migration and polar body extrusion. Here, we report that the vesicle trafficking protein Rab23, a GTPase, drives the motor protein Kif17, and that this is important for spindle organization and actin dynamics during mouse oocyte meiosis. GTP-bound Rab23 accumulated at the spindle and promoted migration of Kif17 to the spindle poles. Depletion of Rab23 or Kif17 caused polar body extrusion failure. Further analysis showed that depletion of Rab23/Kif17 perturbed spindle formation and chromosome alignment, possibly by affecting tubulin acetylation. Kif17 regulated tubulin acetylation by associating with αTAT and Sirt2, and depletion of Kif17 altered expression of these proteins. Moreover, depletion of Kif17 decreased the level of cytoplasmic actin, which abrogated spindle migration to the cortex. The tail domain of Kif17 associated with constituents of the RhoA-ROCK-LIMK-cofilin pathway to modulate assembly of actin filaments. Taken together, our results demonstrate that the Rab23-Kif17-cargo complex regulates tubulin acetylation for spindle organization and drives actin-mediated spindle migration during meiosis.

Keywords: Actin; Kinesin; Meiosis; Microtubule; Mouse; Oocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Actin Depolymerizing Factors / genetics
  • Actin Depolymerizing Factors / metabolism
  • Animals
  • Kinesins / genetics
  • Kinesins / metabolism*
  • Lim Kinases / genetics
  • Lim Kinases / metabolism
  • Meiosis / physiology*
  • Mice
  • Oocytes / cytology
  • Oocytes / metabolism*
  • Signal Transduction / physiology
  • Sirtuin 2 / genetics
  • Sirtuin 2 / metabolism
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism*
  • Tubulin / genetics
  • Tubulin / metabolism*
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism
  • rhoA GTP-Binding Protein

Substances

  • Actin Depolymerizing Factors
  • KIF17 protein, mouse
  • Tubulin
  • Lim Kinases
  • Sirt2 protein, mouse
  • Sirtuin 2
  • Rab23 protein, mouse
  • Kinesins
  • RhoA protein, mouse
  • rab GTP-Binding Proteins
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein