Septin

FRAP analysis has revealed that the turnover of septins at the neck undergoes multiple changes during the cell cycle.

The predominant, functional conformation is characterized by a low turnover rate (frozen state), during which the septins are phosphorylated.

Structural changes require a destabilization of the septin cortex (fluid state) induced by dephosphorylation prior to bud emergence, ring splitting and cell separation.

This polarity of the septin network allows concentration of some proteins primarily to the mother side of the neck, some to the center and others to the bud site.

Budding yeast cytokinesis is driven through two septin dependent, redundant processes: recruitment and contraction of the actomyosin ring and formation of the septum by vesicle fusion with the plasma membrane.

In contrast to septin mutants, disruption of one single pathway only leads to a delay in cytokinesis, not complete failure of cell division.

The septin ring at the neck serves as a cortical barrier that prevents membrane diffusion of these factors between the two compartments.

Since their discovery in S. cerevisiae, septin homologues have been found in other eukaryotic species, including filamentous fungi.

Without Cdc3 and Cdc12 genes Candida albicans cannot proliferate, other septins affect morphology and chitin deposition, but are not essential.

Candida albicans can display different morphologies of vegetative growth, which determines the appearance of septin structures.

Due to the lack of septa, septin deletion mutants are highly sensitive, and damage of a single hypha can result in complete lysis of a young mycelium.

For example, the actin bundling protein anillin is required for correct spatial control of septin organization.

[5] In the sperm cells of mammals, septins form a stable ring called annulus in the tail.

[4][5] In humans, septins are involved in cytokinesis, cilium formation and neurogenesis through the capability to recruit other proteins or serve as a diffusion barrier.

The septin proteins produced by these genes are grouped into four subfamilies each named after its founding member: (i) SEPT2 (SEPT1, SEPT4, SEPT5), (ii) SEPT3 (SEPT9, SEPT12), (iii) SEPT6 (SEPT8, SEPT10, SEPT11, SEPT14), and (iv) SEPT7.

[4][5][1] Septins form cage-like structures around bacterial pathogens, immobilizing harmful microbes and preventing them from invading healthy cells.

Potential therapies for these, as well as for bacterial conditions such as dysentery caused by Shigella, might bolster the body’s immune system with drugs that mimic the behaviour of TNF-α and allow the septin cages to proliferate.

In 1976, analysis of electron micrographs revealed ~20 evenly spaced striations of 10-nm filaments around the mother-bud neck in wild-type but not in septin-mutant cells.

Purified septins from budding yeast, Drosophila, Xenopus, and mammalian cells are able to self associate in vitro to form filaments.

Micrographs of purified filaments raised the possibility that the septins are organized in parallel to the mother-bud axis.