Septin 7 is a centrosomal protein that ensures S phase entry and microtubule nucleation by maintaining the abundance of p150^glued

Abstract

Septins play important roles in regulating development and differentiation. Septin 7 (SEPT7) is a crucial component in orchestrating the septin core complex into highly ordered filamentous structures. Here, we showed that genetic depletion of SEPT7 or treatment with forchlorfenuron (FCF; a compound known to affect septin filament assembly) led to reduced the S phase entry in cell models and zebrafish embryos. In addition to colocalizing with actin filaments, SEPT7 resided in the centrosome, and SEPT7 depletion led to aberrant mitotic spindle pole formation. This mitotic defect was rescued in SEPT7‐deficient cells by wild‐type SEPT7, suggesting that SEPT7 maintained mitotic spindle poles. In addition, we observed disorganized microtubule nucleation and reduced cell migration with SEPT7 depletion. Furthermore, SEPT7 formed a complex with and maintained the abundance of p150glued, the component of centriole subdistal appendages. Depletion of p150glued resulted in a phenotype reminiscent of SEPT7‐deficient cells, and overexpression of p150glued reversed the defective phenotypes. Thus, SEPT7 is a centrosomal protein that maintains proper cell proliferation and microtubule array formation via maintaining the abundance of p150glued.

Cellular functions of actin- and microtubule-associated septins

“…Septins function in the nucleation, organization, dynamics and post-translational modifications of microtubules (Figure 5B-E). SEPT7 and SEPT1 are uniquely involved in the nucleation of microtubules from the centrosome and Golgi complex, respectively (Figure 5B) 108,118 . SEPT7 is required for the centrosomal localization of the dynactin subunit p150 Glued , and SEPT7 depletion results in the nucleation of a more dense and disorganized microtubule network 118 .…”

“…SEPT7 and SEPT1 are uniquely involved in the nucleation of microtubules from the centrosome and Golgi complex, respectively (Figure 5B) 108,118 . SEPT7 is required for the centrosomal localization of the dynactin subunit p150 Glued , and SEPT7 depletion results in the nucleation of a more dense and disorganized microtubule network 118 . On Golgi membranes, SEPT1 interacts with the centrosomal protein CEP170, promoting the nucleation of acentrosomal microtubules 108 .…”

“…Assembly of bipolar mitotic and meiotic spindles requires properly duplicated centrosomes, which nucleate microtubules and are located at the opposing poles of the spindle. Recent work shows that SEPT7 localizes to the centrosome in the absence of SEPT2 and SEPT6 and interacts with p150 Glued , which localizes to the subdistal appendages of centrioles 118 . Indicative of a function in centriole duplication, SEPT7 knockdown causes multipolar spindle formation and consequently impairs chromosome segregation 118 .…”

“…Recent work shows that SEPT7 localizes to the centrosome in the absence of SEPT2 and SEPT6 and interacts with p150 Glued , which localizes to the subdistal appendages of centrioles 118 . Indicative of a function in centriole duplication, SEPT7 knockdown causes multipolar spindle formation and consequently impairs chromosome segregation 118 . SEPT7 also interacts with centromere-associated protein E (CENP-E)/KIF10, a kinesin-7 motor that mediates microtubule attachment to misaligned chromosomes, promoting chromosome alignment and bi-orientation 151 .…”

Etoposide Triggers Cellular Senescence by Inducing Multiple Centrosomes and Primary Cilia in Adrenocortical Tumor Cells

“…Mitotic cells were counted according to our published protocol [30]. In brief, mitotic cells, including cells in the pro-, prometa, meta-, ana-, and telo-phase, were counted in all populations of cells.…”