Kif3a guides microtubular dynamics, migration and lumen formation of MDCK cells

PLoS One. 2013 May 1;8(5):e62165. doi: 10.1371/journal.pone.0062165. Print 2013.

Abstract

The microtubular motor Kinesin-2 and its subunit Kif3a are essential for the formation of primary cilia, an organelle implicated in a wide spectrum of developmental abnormalities. Outside cilia, Kinesin-2 mediated transport has been implicated in vesicle and N-cadherin transport, but it is unknown if and how extraciliary Kif3a affects basic cellular functions such as migration or the formation of multicellular structures. Here we show that tetracycline inducible depletion of Kif3a in MDCK cells slows epithelial cell migration. Microtubules at the leading edge of Kif3a depleted cells failed to grow perpendicularly into the leading edge and microtubular dynamics were dampened in Kif3a depleted cells. Loss of Kif3a retarded lateral membrane specification and completely prevented the formation of three-dimensional spheres in collagen. These data uncover that Kif3a regulates the microtubular cytoskeleton in the cell periphery and imply that extra-ciliary Kif3a has an unexpected function in morphogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Cilia / physiology
  • Dogs
  • Kinesins / physiology*
  • Madin Darby Canine Kidney Cells
  • Microtubules / metabolism*
  • Morphogenesis
  • Protein Multimerization
  • Protein Processing, Post-Translational
  • Spheroids, Cellular / cytology
  • Spheroids, Cellular / metabolism
  • Tight Junctions / metabolism

Substances

  • Kinesins

Grant support

This work was supported by DFG grants KU 1504 (EWK), SFB 592 Z2 (RN) and BIOSS cluster of excellence 294 (RN, EWK, GW). GW is supported by the DFG KFO 201, and by the European Community's Seventh Framework Program (grant agreement number 241955, SYSCILIA). BB is supported by a junior career development grant (J3) of the Interdisciplinary Center of Clinical Research at the University of Erlangen-Nuremberg. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.