Abstract
Septins are cytoskeletal GTPases present in nonpolar heteromeric complexes that assemble in a palindromic fashion from two to eight subunits. Mammalian septins function in several fundamental cellular processes at the membrane-cytoskeleton interface including dendritic branching in neurons. Sequence homology divides the 13 mammalian septin genes into four homology groups. Experimental findings suggest that septin function is redundant among septins from one homology group. This is best understood for the isoforms of the SEPT2 group, which form a homodimer at the center of septin complexes. In vitro, all SEPT2-group septins form recombinant hexameric complexes with two copies of SEPT6 and SEPT7. However, it remains unclear to what extent homologs septins can substitute for each other in specific cellular processes. Here, we use the experimental paradigm of dendritic branching in hippocampal rat neurons to ask, to what extent septins of the SEPT2-group are functionally redundant. Dendritic branching is significantly reduced when SEPT5 is downregulated. In neurons expressing SEPT5-shRNA, simultaneously expressed SEPT2-GFP, and SEPT4-GFP colocalize with SEPT7 at dendritic spine necks and rescue dendritic branching. In contrast, SEPT1-GFP is diffusely distributed in the cytoplasm in SEPT5 downregulated neurons and cannot rescue dendritic branching. Our findings provide a basis for the study of septin-specific functions in cells.
Highlights
The septins are a family of conserved GTPases present in all eukaryotes except land plants and have first been described as cell division cycle mutants in yeast (Hartwell, 1971)
In cultured rat hippocampal neurons, a complex consisting of SEPT5, SEPT7, and SEPT11 has been reported to coimmunoprecipitate and to localize to dendritic branching points (Tada et al, 2007; Garcia et al, 2011)
Septin complexes are assembled from several different septins from the four groups classified by sequence homology in dependence on their tissue-specific expression
Summary
The septins are a family of conserved GTPases present in all eukaryotes except land plants and have first been described as cell division cycle (cdc) mutants in yeast (Hartwell, 1971). The function of many septins may be redundant to a certain extent, since knockout mice of SEPT3, 4, 5, and 6 show no detectable or very specific defects (Peng et al, 2002; Ono et al, 2005; Fujishima et al, 2007; Tsang et al, 2008). The knockout of certain septin genes induced an upregulation in protein expression levels of others in the same homology group. These findings suggest a possible functional redundancy between septin genes (Peng et al, 2002). SEPT7 and SEPT9 on the other hand seem to be essential since the respective knockouts are embryonic lethal in mice (Füchtbauer et al, 2011; Menon et al, 2014)
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