Role of Septins

Septins are the fourth major protein component of the cytoskeleton, alongside microfilaments, microtubules, and intermediate filaments. These proteins can associate with other cytoskeletal filaments or exist freely in the cytoplasm. Septins function as scaffolds that promote protein-protein interactions and carry out diverse roles in cellular processes including cytokinesis, ciliogenesis, and neurogenesis.

In neurons, septins function as microtubule-associated proteins that bind with microtubules to regulate vesicle trafficking. They coordinate with motor proteins including kinesins to control the movement of cargo transport along microtubules. This interaction enables efficient delivery of organelles and vesicles throughout the neuron.

During cytokinesis, septins identify the cleavage furrow in the plasma membrane and form a septin ring around it. This ring recruits structural proteins like microfilaments and myosin II filaments to assemble the contractile ring. The contractile ring then drives the physical separation of daughter cells during cell division.

During cilia formation, septins detect the outward curvature of the plasma membrane and interact to form a diffusion barrier at the cilium base. This barrier selectively controls the transport of solute particles between the cilium and the cytoplasm, maintaining distinct chemical environments. This compartmentalization is essential for proper ciliary function and motility.

Mutations in septin-forming genes like SEPT12 significantly affect sperm motility and structural integrity. Septins were first discovered in the sperm flagella's annulus, which compartmentalizes the anterior and posterior tail regions. Defective septins compromise the flagellar architecture necessary for proper sperm movement and fertilization.

Studies show septins are associated with proteins involved in neurodegenerative diseases like Parkinson's and Alzheimer's. In Parkinson's disease, septins interact with parkin, an E3 ubiquitin ligase involved in protein degradation pathways. Understanding these septin interactions may reveal therapeutic targets for treating neurodegeneration.

Septin mutations have been linked to tumorigenesis and cancer progression. Research on cancerous cells indicates that septin mutations correlate with increased cell resistance, metastasis, proliferation, and angiogenesis. These findings suggest septins play critical roles in maintaining normal cell growth control and preventing malignant transformation.