Decoding post‐translational modifications of mammalian septins

Abstract

Septins are cytoskeletal GTPases that form nonpolar filaments and higher‐ordered structures and they take part in a wide range of cellular processes. Septins are conserved from yeast to mammals but absent from higher plants. The number of septin genes vary between organisms and they usually form complex heteropolymeric networks. Most septins are known to be capable of GTP hydrolysis which may regulate septin dynamics. Knowledge on regulation of septin function by post‐translational modifications is still in its infancy. In this review article, we highlight the post‐translational modifications reported for the 13 human septins and discuss their implications on septin functions. In addition to the functionally investigated modifications, we also try to make sense of the complex septin post‐translational modification code revealed from large‐scale phospho‐proteomic datasets. Future studies may determine how these isoform‐specific and homology group specific modifications affect septin structure and function.

The Roles of Septins in Regulating Fission Yeast Cytokinesis

“…In addition to Cla4 and Gin4, several other kinases, including Kcc4 [87], Hsl1 [88], and Elm1 [89,90], have been reported to interact with septins and regulate the structural transition and organization of septins. Phosphorylation is the most frequently reported modification of mammalian septins, which is involved in regulating cytokinesis, sperm annulus organization, neuronal morphogenesis, and post-synaptic stability [91]. Whether and how fission yeast septins are regulated by phosphorylation await further investigation.…”

Septins function in exocytosis via physical interactions with the exocyst complex in fission yeast cytokinesis

“…In addition, tests are needed to figure out if posttranslational modifications are necessary for the interactions between septins and the exocyst. Because the colocalization of septins and the exocyst required for their proper function occurs at a specific stage during cytokinesis rather than a general regulation throughout the cell cycle, septin filament formation and posttranslational modifications of the involved proteins may be required, which make it challenging to tease out the interactions in vitro (Dobbelaere et al, 2003;Hernández-Rodríguez and Momany, 2012;Ren and Guo, 2012;Tay et al, 2019;Sharma and Menon, 2023;Werner and Yadav, 2023). Moreover, we cannot rule out that RhoA GTPase and PI(4,5)P2 are involved in septin-exocyst interactions as both has been reported to interact with septins and/or the exocyst in other cell types (Guo et al, 2001;He et al, 2007;Bertin et al, 2010;Bendezu and Martin, 2011;Perez et al, 2015;Carim and Hickson, 2023;Safavian et al, 2023).…”

Introduction to the Special Issue of Cytoskeleton on the molecular and cell biology of septins

“…The role of post‐translational modifications (including ubiquitylation, SUMOylation, phosphorylation and acetylation) in septin biology has been of great interest for many years. In a review, Sharma and Menon (2023) discuss post‐translational modifications of human septins and how this may impact their function. The BORG/Cdc42EP family, composed of five Rho GTPase binding proteins, is of historical interest to the field because of their fundamental interplay with the septin cytoskeleton.…”