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

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 corti-cal 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 fila-ment, 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.SignificanceTight regulation of cytoskeletal remodeling is essential for various neurodevelopmental processes. The microtubule and actin crosstalk to accomplish dynamic rearrangement of the cytoskeleton. Here, we reveal that granule cell antiserum-positive 14 (Gcap14) functions as a microtubule plus-end-tracking protein modulating microtubule dynamics. These processes are achieved by Gcap14 in complex with Ndel1, which functionally links the microtubule and actin cytoskeleton. Successful linkage of growing microtubules to actin filament requires the Gcap14- Ndel1 complex in the growth cones of developing neurons, underlying the proper neuronal migration and cortical lamination. These findings provide fundamental mechanistic insights into the cytoskeletal dynamics regulation required for key neurodevelopment steps.

Automated summary

In this study, the Gcap14-Ndel1 complex is identified as a fundamental regulator of cytoskeletal remodeling during neurodevelopment, including neuronal process elongation and migration. Deficiency of Gcap14 leads to impaired cortical lamination and defective neuronal migration. The interaction between Gcap14 and Ndel1 effectively corrects the downregulation of microtubule dynamics and the defects in neuronal migration caused by Gcap14 deficiency.