Abstract:
Kaptin, whose mutations cause the kaptin-related disorder, is part of the KICSTOR complex that inhibits the mTORC1 pathway. Additionally, kaptin was recently discovered to function as a capping protein on actin filaments. A heteroallelic kaptin knockout model established in the lab shows increased axon collateral branches in motor neurons and a decreased latency to seizures during development compared with wild type. From studies in our lab, the hyperbranching phenotype has been attributed to kaptin’s regulation of actin, but very little is known about the possibility of dysregulation of the mTORC1 pathway. The decreased latency to seizures could be attributed to possible hyperbranching in CNS neurons or aberrant mTORC1 signalling, which has been implicated in seizures. This study investigates the presence of a cellular/organ-level overgrowth phenotype, associated with mTORC1 hyperactivity, in the nervous system of developing kaptin knockout zebrafish embryos. In assessments of the spinal cord using cell area and overall spinal cord area analyses, mutant larvae did not exhibit an overgrowth phenotype compared with wild-type larvae. Our study questions the role of kaptin in the mTORC1 pathway during nervous system development. It draws attention to the possibility of phylogenetic changes in the function of the KICSTOR complex, which is conserved across vertebrates during development.
