Septins 2, 7, and 9 and MAP4 co-localize along the axoneme in the primary cilium and control ciliary length

Abstract

SummarySeptins are a large, evolutionarily conserved family of GTPases that form hetero-oligomers and interact with the actin-based cytoskeleton and microtubules. They are involved in scaffolding functions, and form diffusion barriers in budding yeast, the sperm flagellum and the base of primary cilia of kidney epithelial cells. We investigated the role of septins in the primary cilium of retinal pigmented epithelial (RPE) cells, and found that SEPT2 forms a 1:1:1 complex with SEPT7 and SEPT9 and that the three members of this complex colocalize along the length of the axoneme. Similar to observations in kidney epithelial cells, depletion of cilium-localized septins by siRNA-based approaches inhibited ciliogenesis. MAP4, which is a binding partner of SEPT2 and controls the accessibility of septins to microtubules, was also localized to the axoneme where it appeared to negatively regulate ciliary length. Taken together, our data provide new insights into the functions and regulation of septins and MAP4 in the organization of the primary cilium and microtubule-based activities in cells.

Septin oligomerization regulates persistent expression of ErbB2/HER2 in gastric cancer cells

“…Septin-9 levels were also moderately decreased (Fig. 4A), presumably due to posttranslational down-regulation, consistent with known coordinated regulation of levels of individual septins [63]. Septin knockdown resulted in an almost 2-fold decrease in ErbB2 protein without affecting EGFR levels (Fig.…”

Sept6 Is Required for Ciliogenesis in Kupffer's Vesicle, the Pronephros, and the Neural Tube during Early Embryonic Development

“…Despite extensive characterization of some septin complexes in vitro, the composition and size of septin complexes in specific cell types or tissues remain largely unknown. While our manuscript was under revision, the mammalian SEPT2/7/9 complex was reported to colocalize with ciliary microtubules and to control ciliary length in RPE cells (26). In addition, FCF, an inhibitor of septin assembly and organization, affects ciliogenesis and LR patterning of visceral organs (this study).…”

“…These septin rings are thought to act as diffusion barriers for maintaining distinct membrane domains. Recently, SEPT2/7/9 were reported to localize along the axoneme in the primary cilia of retinal pigmented epithelial (RPE) cells and to regulate ciliary length (26). However, the role of septins in ciliogenesis in the context of vertebrate development has not been extensively explored.…”

СЕПТИНОВЫЕ КОМПЛЕКСЫ И?ДИНАМИКА ЦИТОСКЕЛЕТА, "Молекулярная Биология"

“…3c). SEPT2, SEPT7, or SEPT9 depletion in human retinal pigmented epithelial cells (RPE1), which represent a canonical model for study of primary cilia, resulted in shortening of cilia and decrease in their number [99]. SEPT2 depletion in kidney epithelial cells or in mouse embryonic fibroblasts leads to enhanced diffusion of membrane proteins between cilia and the remaining cell membrane, which demonstrates the importance of the septin diffusion barrier in ciliogenesis [100].…”