{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSEPTIN3 is a member of the septin family of GTP‐binding proteins, which assemble into filamentous structures that serve roles in cellular compartmentalization, scaffolding, and regulation of cytoskeletal dynamics. In mammals, septins are divided into distinct subgroups, and SEPTIN3 belongs to the subgroup that is especially enriched in neuronal tissues, suggesting a specialized role in vesicle trafficking, neurite outgrowth, and possibly synaptic organization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural studies of SEPTIN3 have provided key insights into its molecular properties. A crystal structure of a construct encompassing its GTP‐binding and C‐terminal domains revealed that SEPTIN3 purified as a nucleotide‐free monomer, yet in the crystal it assembled into foreshortened filaments through interfaces similar to those seen in heterotrimeric complexes of other septins. This observation reinforces the idea that septins can engage in “promiscuous” interactions via conserved NC and G interfaces, thus contributing to the diverse architecture and regulation of septin filament assembly."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional analyses further suggest that SEPTIN3 plays a role in normal neuronal physiology and may be implicated in neurological disorders. Expression studies indicate that isoforms A and B of SEPTIN3 are present in both fetal and adult human brain, and genetic polymorphism in SEPTIN3 (notably in exon 11) has been linked to altered risk for Alzheimer’s disease, with a lower frequency of the short allele in patients. In addition, in silico docking studies using the small molecule forchlorfenuron (FCF) have shown that SEPTIN3, along with other septins, possesses conserved nucleotide‐binding motifs that interact with FCF. These interactions appear to lock septin proteins in a conformation that mimics a nucleotide‐bound state, thereby stabilizing septin filaments and suggesting a pathway through which septin dynamics may be pharmacologically modulated."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Masanori Takehashi, Tyler Alioto, Todd Stedeford, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Septin 3 gene polymorphism in Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene Expr (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3727/000000003783992243"}], "href": "https://doi.org/10.3727/000000003783992243"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15200238"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15200238"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Joci N A Macedo, Napoleão F Valadares, Ivo A Marques, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The structure and properties of septin 3: a possible missing link in septin filament formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20120851"}], "href": "https://doi.org/10.1042/BJ20120851"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23163726"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23163726"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Dimitrios Angelis, Eva Pauline Karasmanis, Xiaobo Bai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "In silico docking of forchlorfenuron (FCF) to septins suggests that FCF interferes with GTP binding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0096390"}], "href": "https://doi.org/10.1371/journal.pone.0096390"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24787956"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24787956"}]}]}]}