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

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.

CCSer2 gates dynein activity at the cell periphery

“…When imaged live, as was observed with the mouse homologue, CCSer2 WT displayed many dynamic, comet-like structures reminiscent of proteins that track microtubule plus-ends (+Tips) (Figure 1H, Supplemental movie-1). 33 Consistent with microtubule plus-end localization, CCSer2 WT puncta colocalized with the master plus-end regulator, EB1 (Figure S2B). Indeed, CCSer2 contains four EB1-binding S-x-I/L-P motifs, where “x” corresponds to any amino acid (Figure S2C).…”

“…In ccser2a;ccser2b double heterozygous crosses, double mutant offspring survived at sub-mendelian ratios, consistent with the loss of the ccser2 homologue in mouse litters (Figure S3C). 33 However, surviving double mutant animals were grossly normal. This bimodal effect, where the double mutant is lethal in most embryos but escapers are healthy, is likely due to variable genetic compensation by ccser2 ’s paralog, ccser1 because in stable mutant zebrafish lines, paralogs are often upregulated to compensate for genetic deletion.…”

Multiple Genes with Potential Tumor Suppressive Activity Are Present on Chromosome 10q Loss in Neuroblastoma and Are Associated with Poor Prognosis

“…What is interesting is that the protein DISC1 is involved in human NB cells regulating the activation of PI3K [ 39 , 40 ]. Furthermore, CCSER2 is a regulator of microtubule dynamics during neurodevelopment, and its deficiency results in defective neuronal migration [ 41 ]. CCSER2 has not yet been described as a tumor suppressor gene, however, there is a good chance that it could be involved in the development or progression of NB, even if functional studies will be needed to define this role.…”

The effects of chronic morphine administration on spatial memory and microtubule dynamicity in male mice's brain

“…Numerous studies have explored the correlation between microtubule dynamicity, learning, and memory. Microtubule dynamicity denotes their capacity for rapid alterations in length and orientation, critical for diverse neuronal processes such as axonal growth and synaptic remodeling ( Mun et al, 2023 , Waites et al, 2021 ).…”