Phosphoregulation of the septin cytoskeleton in neuronal development and disease

Septins are highly conserved GTP-binding proteins that oligomerize and form higher order structures. The septin cytoskeleton plays an important role in cellular organization, intracellular transport, and cytokinesis. Kinase-mediated phosphorylation of septins regulates various aspects of their function, localization, and dynamics. Septins are enriched in the mammalian nervous system where they contribute to neurodevelopment and neuronal function. Emerging research has implicated aberrant changes in septin cytoskeleton in several human diseases. The mechanisms through which aberrant phosphorylation by kinases contributes to septin dysfunction in neurological disorders are poorly understood and represent an important question for future research with therapeutic implications. This review summarizes the current state of knowledge of the diversity of kinases that interact with and phosphorylate mammalian septins, delineates how phosphoregulation impacts septin dynamics, and describes how aberrant septin phosphorylation contributes to neurological disorders.