Right place, right time - Spatial guidance of neuronal morphogenesis by septin GTPases

Pyramidal neuron morphogenesis requires a septin network that stabilizes filopodia and suppresses lamellipodia during neurite initiation

“…Septins are essential components of neuronal morphogenesis with roles in axodendritic development and the formation of axon branches, and dendritic spines (Radler and Spiliotis, 2022; Tada, et al, 2007). In differentiating neural crest cells, septins determine the cortical sites of neurite re-emergence after mitosis, but how septins function in neurite initiation is not understood (Boubakar, et al, 2017).…”

“…Septins have evolutionarily conserved roles in cellular morphogenesis and the spatial organization of membrane and cytoskeletal proteins (Spiliotis and Nakos, 2021; Caudron and Barral, 2009). In neurons, septins have been functionally linked to axodendritic growth and branching, dendritic spine maturation and polarized membrane traffic (Radler and Spiliotis, 2022; Ageta-Ishihara and Kinoshita, 2021). Septin 7 (Sept7), a ubiquitous and obligate subunit of heteromeric septin complexes, was notably found to provide a spatial memory for the post-mitotic reemergence of neurites in neural crest cells (Boubakar, et al, 2017).…”

Septins as membrane influencers: direct play or in association with other cytoskeleton partners

“…In neurons, septin-mediated polarity establishment occurs through membrane compartmentalization processes (Radler and Spiliotis, 2022). For example, septins demarcate the cortical sites of neurite retraction before mitosis to ensure their proper reemergence location in daughter neurons, thereby maintaining polarity inheritance (Boubakar et al, 2017).…”

Phosphoregulation of the septin cytoskeleton in neuronal development and disease

“…Even though most septins are expressed almost ubiquitously across mammalian cell types, many are highly expressed in the central nervous system and play crucial roles in its development and maintenance (Hall et al, 2005). While the underlying mechanisms of septin function in neurodevelopmental processes remain largely underexplored, known roles primarily involve structural support and barrier formation, positive or negative regulation of actin and microtubule cytoskeletons, and regulation of membrane trafficking (Ageta‐Ishihara & Kinoshita, 2021; Radler & Spiliotis, 2022). This is achieved through their ability to scaffold histone‐ and protein‐modifiers, guide the localization of cytoskeletal components, recruit other cytoskeleton and membrane‐associated proteins, and form higher‐order structures (Ageta‐Ishihara et al, 2013; Ageta‐Ishihara & Kinoshita, 2021; Brand et al, 2012; Hu et al, 2012; Radler & Spiliotis, 2022).…”

“…Aberrant cytoskeleton phosphoregulation in metazoans remains ambiguous despite its physiological relevance and association with various neurological disorders (Muñoz‐Lasso et al, 2020; Rudrabhatla et al, 2011). Many human septins are enriched in the nervous system and play major developmental and post‐developmental roles in the brain in which they associate with kinases and other phosphorylated cytoskeletal proteins (Ageta‐Ishihara & Kinoshita, 2021; Radler & Spiliotis, 2022); however, mammalian septin phosphoregulation in this neuronal context is poorly understood. Herein, we review kinases associated with mammalian septins and their phosphorylation sites and describe trends in site localization and the conserved nature of septin phosphoregulation.…”