Expression of integrins to control migration direction of electrotaxis

FASEB J. 2019 Aug;33(8):9131-9141. doi: 10.1096/fj.201802657R. Epub 2019 May 22.

Abstract

Proper control of cell migration is critically important in many biologic processes, such as wound healing, immune surveillance, and development. Much progress has been made in the initiation of cell migration; however, little is known about termination and sometimes directional reversal. During active cell migration, as in wound healing, development, and immune surveillance, the integrin expression profile undergoes drastic changes. Here, we uncovered the extensive regulatory and even opposing roles of integrins in directional cell migration in electric fields (EFs), a potentially important endogenous guidance mechanism. We established cell lines that stably express specific integrins and determined their responses to applied EFs with a high throughput screen. Expression of specific integrins drove cells to migrate to the cathode or to the anode or to lose migration direction. Cells expressing αMβ2, β1, α2, αIIbβ3, and α5 migrated to the cathode, whereas cells expressing β3, α6, and α9 migrated to the anode. Cells expressing α4, αV, and α6β4 lost directional electrotaxis. Manipulation of α9 molecules, one of the molecular directional switches, suggested that the intracellular domain is critical for the directional reversal. These data revealed an unreported role for integrins in controlling stop, go, and reversal activity of directional migration of mammalian cells in EFs, which might ensure that cells reach their final destination with well-controlled speed and direction.-Zhu, K., Takada, Y., Nakajima, K., Sun, Y., Jiang, J., Zhang, Y., Zeng, Q., Takada, Y., Zhao, M. Expression of integrins to control migration direction of electrotaxis.

Keywords: directional cell migration; directional reversal; galvanotaxis; motility; α9.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • CHO Cells
  • Cell Movement / genetics
  • Cell Movement / physiology*
  • Cricetulus
  • Electricity
  • Fluorescent Dyes
  • Humans
  • Integrin alpha Chains / genetics
  • Integrin alpha Chains / physiology
  • Integrins / genetics
  • Integrins / physiology*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Taxis Response / physiology
  • Time-Lapse Imaging
  • Transcriptome

Substances

  • Fluorescent Dyes
  • Integrin alpha Chains
  • Integrins
  • Recombinant Proteins
  • integrin alpha9