Role of Septin Cytoskeleton in Spine Morphogenesis and Dendrite Development in Neurons

Abstract

Septins are GTP-binding proteins that polymerize into heteromeric filaments and form microscopic bundles or ring structures in vitro and in vivo. Because of these properties and their ability to associate with membrane, F-actin, and microtubules, septins have been generally regarded as cytoskeletal components [1, 2]. Septins are known to play roles in cytokinesis, in membrane trafficking, and as structural scaffolds; however, their function in neurons is poorly understood. Many members of the septin family, including Septin 7 (Sept7), were found by mass-spectrometry analysis of postsynaptic density (PSD) fractions of the brain [3, 4], suggesting a possible postsynaptic function of septins in neurons. We report that Sept7 is localized at the base of dendritic protrusions and at dendritic branch points in cultured hippocampal neurons--a distribution reminiscent of septin localization in the bud neck of budding yeast. Overexpression of Sept7 increased dendrite branching and the density of dendritic protrusions, whereas RNA interference (RNAi)-mediated knockdown of Sept7 led to reduced dendrite arborization and a greater proportion of immature protrusions. These data suggest that Sept7 is critical for spine morphogenesis and dendrite development during neuronal maturation.

Septin 11 Is Present in GABAergic Synapses and Plays a Functional Role in the Cytoarchitecture of Neurons and GABAergic Synaptic Connectivity

“…In neurons, septin 11 forms heterooligomeric complexes with septin 7 and septin 5 (9,18). Nevertheless, the regional and developmental distribution of septin 11 in the brain and in hippocampal cultures is not identical to that of septin 7 or septin 5 (8). These results and other heterooligomerization studies show that septin 11 is not always associated with septin 7 and septin 5 (7,15,19).…”

“…Each septin gene is expressed in several spliced forms. Although most septins are highly expressed in the brain (6), only recently is their role in neuronal function (7)(8)(9) and in neuropathology (10 -14) is beginning to be addressed for some septins.…”

Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

“…As the morphology of the Golgi complex depends to a large extent on the integrity of the surrounding cytoskeletal elements (Bard and Malhotra, 2006;Egea et al, 2006;De Matteis and Luini, 2008), the observed disruption of the Golgi complex could be also a consequence of altered cytoskeletal organization upon kdPKD1 expression. Additionally, cytoskeletal rearrangements fundamentally influence the formation and maintenance of dendritic structures, including elongation and branching of dendrites or spine formation (Gauthier-Campbell et al, 2004;Kim et al, 2006;Hayashi et al, 2007;Tada et al, 2007;Zhang and Macara, 2008). Accordingly, direct or indirect cytoskeletal effects of PKD can also participate in the observed dendritic rearrangements in transfected neurons, especially when taking into account that high level of PKD activity was observed not only around the neuronal Golgi but also in the cytoplasm of dendrites and even in the dendritic spines.…”

Yeast and fungal morphogenesis from an evolutionary perspective

“…The septins also serve as a diffusion barrier between the bud and mother cortex, which in turn is required for the asymmetric distribution of several proteins involved in mitotic exit and cell polarization [47,48]. Interestingly, a recent paper reported that the septins are localized at the bases of "budlike" dendritic spines in hippocampal neurons and are important for dendritic spine development [49]. This finding suggests that septins' role in morphogenesis may be conserved between fungi and animal cells.…”