The GTP-Binding Protein Septin 7 Is Critical for Dendrite Branching and Dendritic-Spine Morphology

Abstract

Septins, a highly conserved family of GTP-binding proteins, were originally identified in a genetic screen for S. cerevisiae mutants defective in cytokinesis [1, 2]. In yeast, septins maintain the compartmentalization of the yeast plasma membrane during cell division by forming rings at the cortex of the bud neck, and these rings establish a lateral diffusion barrier. In contrast, very little is known about the functions of septins in mammalian cells [3, 4] including postmitotic neurons [5-7]. Here, we show that Septin 7 (Sept7) localizes at the bases of filopodia and at branch points in developing hippocampal neurons. Upon downregulation of Sept7, dendritic branching is impaired. In mature neurons, Sept7 is found at the bases of dendritic spines where it associates with the plasma membrane. Mature Sept7-deficient neurons display elongated spines. Furthermore, Sept5 and Sept11 colocalize with and coimmunoprecipitate with Sept7, thereby arguing for the existence of a Septin5/7/11 complex. Taken together, our findings show an important role for Sept7 in regulating dendritic branching and dendritic-spine morphology. Our observations concur with data from yeast, in which downregulation of septins yields elongated buds, suggesting a conserved function for septins from yeast to mammals.

High-resolution SNP arrays in mental retardation diagnostics: how much do we gain?

“…shown to be expressed in CNS, both in cell bodies and dendrites, 41,42 and septins are GTP-binding proteins interacting with developing myelin structures. 43 No mosaic genomic alteration was found in our cohort of patients, either indicating that mosaic imbalances are a very rare cause of MR/ MCA or reflecting the low sensitivity of the SNP array platform to detect CNVs in samples containing different cell populations.…”

Septin 11 Restricts InlB-mediated Invasion by Listeria

“…In the SEPT7-SEPT6-SEPT2-SEPT2-SEPT6-SEPT7 complex, SEPT2 has a central role in filament formation (9), whereas SEPT6 is thought to be replaceable with other SEPT6 group members, including SEPT11 (3). Widely expressed in mammalian tissues (10), SEPT11 may also be a substitute for SEPT6 in other mammalian septin complexes such as SEPT7-SEPT9-SEPT11 (10) or SEPT5-SEPT7-SEPT11 (11). Because other septins homologous to SEPT11 might compensate for its deficiency (12), the degree to which SEPT11 is required for septin filament structure and function is not yet known.…”

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

“…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.…”

“…Septins 3,5,6, and 7 are localized in the presynaptic terminals, frequently associated with synaptic vesicles (6,16,17). 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).…”

“…In the present paper, we show that septin 11 is associated with the GABAergic synapses, particularly with the postsynapse, and concentrates at the neck of dendritic spines in the intact brain. Others have recently shown that another septin (septin 7) accumulates at the base of dendritic protrusions of cultured neurons (8,9). However, it is not known whether septins also accumulate at the base of the dendritic spines in the brain.…”