Gcap14 is a microtubule plus-end-tracking protein coordinating microtubule-actin crosstalk during neurodevelopment

Proc Natl Acad Sci U S A. 2023 Feb 21;120(8):e2214507120. doi: 10.1073/pnas.2214507120. Epub 2023 Feb 16.

Abstract

Regulation of microtubule dynamics is required to properly control various steps of neurodevelopment. In this study, we identified granule cell antiserum-positive 14 (Gcap14) as a microtubule plus-end-tracking protein and as a regulator of microtubule dynamics during neurodevelopment. Gcap14 knockout mice exhibited impaired cortical lamination. Gcap14 deficiency resulted in defective neuronal migration. Moreover, nuclear distribution element nudE-like 1 (Ndel1), an interacting partner of Gcap14, effectively corrected the downregulation of microtubule dynamics and the defects in neuronal migration caused by Gcap14 deficiency. Finally, we found that the Gcap14-Ndel1 complex participates in the functional link between microtubule and actin filament, thereby regulating their crosstalks in the growth cones of cortical neurons. Taken together, we propose that the Gcap14-Ndel1 complex is fundamental for cytoskeletal remodeling during neurodevelopmental processes such as neuronal processes elongation and neuronal migration.

Keywords: microtubule dynamics; microtubule plus-end-tracking protein; microtubule–actin crosstalk; neurodevelopment; neuronal migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins* / metabolism
  • Animals
  • Cell Movement / physiology
  • Mice
  • Mice, Knockout
  • Microtubule-Associated Proteins* / genetics
  • Microtubule-Associated Proteins* / metabolism
  • Microtubules / metabolism
  • Neurites / metabolism
  • Neurons* / metabolism

Substances

  • Actins
  • Microtubule-Associated Proteins