Disease relevance of Sept2

• Moreover, IgG immunoreactivity to Nedd5 C-ter was significantly higher in patients with systemic sclerosis than in patients of group B or healthy subjects (0.18 +/- 0.18 vs, respectively, 0.11 +/- 0.07, P = 0.046; and 0.09 +/- 0.045, P = 0.003) [1].
• The mean optical density value for IgG immunoreactivity to Nedd5 C-ter was significantly higher in patients of group A than in those of group B, those with infectious mononucleosis, or healthy subjects (0.17 +/- 0.14 vs, respectively, 0.11 +/- 0.07, P = 0.04; 0.11 +/- 0.06, P = 0.034; and 0.09 +/- 0.045, P = 0.003, on Student's t-test) [1].

High impact information on Sept2

• In interphase and postmitotic cells, Nedd5 localizes to fibrous or granular structures depending on the growth state of the cell [2].
• Nedd5 accumulates near the contractile ring from anaphase through telophase, and finally condenses into the midbody [2].
• The Nedd5-containing fibers are disrupted by microinjection of GTPgammaS and by Nedd5 mutants lacking GTP-binding activity, implying that GTP hydrolysis is required for its assembly [2].
• These included changes on Crkl, Ras-GAP-binding protein 1, and for BCR/ABL, cytoskeletal proteins such as tubulin, and Nedd5 [3].
• Thus Sept2 may regulate GLAST-mediated glutamate uptake by astrocytes, which is important for appropriate transmitter signalling in the cerebellum [4].

Biological context of Sept2

• By screening a cDNA library from human umbilical artery endothelial cells with serum from an SLE patient with psychosis, we identified one positive strongly reactive clone encoding the C-terminal region (C-ter) of Nedd5, an intracytoplasmatic protein of the septin family [1].

Anatomical context of Sept2

• The present study revealed that Sept2 co-localizes with the astrocyte glutamate transporter GLAST in the Bergmann glial processes facing axons and synapses [4].
• Nedd5 predominantly localizes with stress fibers, but only associates with central portions of the microfilament bundles [5].
• Conditions that disrupt the actin cytoskeleton also disrupt the filamentous patterns of both Nedd5 and H5, resulting in a punctate cytoplasmic pattern [5].
• H5, like Nedd5, localizes to the cleavage furrow in mitotic fibroblast cells but in non-mitotic cells these proteins associate with actin filaments in different ways [5].
• In order to clarify a possible mechanism by which Nedd5 might be autoantigenic, we observed that Nedd5 relocated from cytoplasm to the plasma membrane of EAhy926 endothelial cells after apoptotic stimuli [1].

Physical interactions of Sept2

• Biochemical analyses demonstrated that Sept2 bound directly to the carboxy-terminal region of GLAST in a GDP-form dependent manner [4].

Other interactions of Sept2

• Expression of constitutive GDP-form Sept2 mutant reduced the glutamate uptake activity of GLAST via internalization of GLAST from cell surface [4].

Analytical, diagnostic and therapeutic context of Sept2

• Microinjection of anti-Nedd5 antibody interferes with cytokinesis, giving rise to binucleated cells [2].
• Immunoelectron microscopy revealed that Nedd5 localized to the paired helical filaments [6].
• Cell fractionation revealed that H5 co-fractionated with actin, while Nedd5 was predominantly restricted to the membrane fraction [5].

References