Phosphoregulation of the septin cytoskeleton in neuronal development and disease

Werner, Bailey; Yadav, Smita

doi:10.1002/cm.21728

Cited by 11 publications

(6 citation statements)

References 138 publications

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“…It has been a mystery why the phenotypes of septin mutants are so mild in fission yeast ever since their discoveries in the early 1990s, yet their sequences and structures are evolutionarily conserved across species (An et al, 2004;Zheng et al, 2018;Zheng et al, 2024). In human, dysregulation of septins or exocyst complex leads to severe disorders including neurological diseases and cancers (Russell and Hall, 2005;Martin-Urdiroz et al, 2016;Halim et al, 2023;Werner and Yadav, 2023). Thus, it is critical to identify the functional links between septins and exocyst complex for better understanding and treatment of related diseases.…”

Section: Discussionmentioning

confidence: 99%

Septins function in exocytosis via physical interactions with the exocyst complex in fission yeast cytokinesis

Singh,

Liu,

Zhu

et al. 2024

Preprint

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Septins can function as scaffolds for protein recruitment, membrane-bound diffusion barriers, or membrane curvature sensors. Septins are important for cytokinesis, but their exact roles are still obscure. In fission yeast, four septins (Spn1 to Spn4) accumulate at the rim of the division plane as rings. The octameric exocyst complex, which tethers exocytic vesicles to the plasma membrane, exhibits a similar localization and is essential for plasma membrane deposition during cytokinesis. Without septins, the exocyst spreads across the division plane but absent from the rim during septum formation. These results suggest that septins and the exocyst physically interact for proper localization. Indeed, we predicted six pairs of direct interactions between septin and exocyst subunits by AlphaFold2 ColabFold, most of them are confirmed by co-immunoprecipitation and yeast two-hybrid assays. Exocyst mislocalization results in mistargeting of secretory vesicles and their cargos, which leads to cell-separation delay in septin mutants. Our results indicate that septins guide the targeting of exocyst complex on the plasma membrane for vesicle tethering during cytokinesis through direct physical interactions.

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Section: Discussionmentioning

confidence: 99%

Septins function in exocytosis via physical interactions with the exocyst complex in fission yeast cytokinesis

Singh,

Liu,

Zhu

et al. 2024

Preprint

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“…com/article/10.3390/ijms241914634/s1. References [72,78,79,124,125,[177][178][179][180][181][182][183][184][185][186][187][188][189] are cited in the Supplementary Materials.…”

Section: Discussionmentioning

confidence: 99%

Nicotine Exposure in a Phencyclidine-Induced Mice Model of Schizophrenia: Sex-Selective Medial Prefrontal Cortex Protein Markers of the Combined Insults in Adolescent Mice

Rodríguez-Vega,

Dutra-Tavares,

Souza

et al. 2023

IJMS

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Tobacco misuse as a comorbidity of schizophrenia is frequently established during adolescence. However, comorbidity markers are still missing. Here, the method of label-free proteomics was used to identify deregulated proteins in the medial prefrontal cortex (prelimbic and infralimbic) of male and female mice modelled to schizophrenia with a history of nicotine exposure during adolescence. Phencyclidine (PCP), used to model schizophrenia (SCHZ), was combined with an established model of nicotine minipump infusions (NIC). The combined insults led to worse outcomes than each insult separately when considering the absolute number of deregulated proteins and that of exclusively deregulated ones. Partially shared Reactome pathways between sexes and between PCP, NIC and PCPNIC groups indicate functional overlaps. Distinctively, proteins differentially expressed exclusively in PCPNIC mice reveal unique effects associated with the comorbidity model. Interactome maps of these proteins identified sex-selective subnetworks, within which some proteins stood out: for females, peptidyl-prolyl cis-trans isomerase (Fkbp1a) and heat shock 70 kDa protein 1B (Hspa1b), both components of the oxidative stress subnetwork, and gamma-enolase (Eno2), a component of the energy metabolism subnetwork; and for males, amphiphysin (Amph), a component of the synaptic transmission subnetwork. These are proposed to be further investigated and validated as markers of the combined insult during adolescence.

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“…Additionally, the increase in SEPTIN proteins in B27 treatment suggests changes in the neurodevelopment realm. SEPTIN proteins contribute to neurodevelopment and neuronal functions in the mammalian nervous system [64], with SEPTIN3 being highly expressed in the brain [65]. SEPTIN3 protein is involved in presynaptic plasticity via the cGMP/PKG pathway, and its expression is developmentally regulated as nervous system development increases [65] and it is predominantly abundant in nerve terminals and presynaptic and synaptic vesicles [65,66].…”

Section: Proteome Changes Unique To B27 Treatmentmentioning

confidence: 99%

Neural Marker Expression in Adipose-Derived Stem Cells Grown in PEG-Based 3D Matrix Is Enhanced in the Presence of B27 and CultureOne Supplements

Gomila Pelegri,

Stanczak,

Bottomley

et al. 2023

IJMS

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Adipose-derived stem cells (ADSCs) have incredible potential as an avenue to better understand and treat neurological disorders. While they have been successfully differentiated into neural stem cells and neurons, most such protocols involve 2D environments, which are not representative of in vivo physiology. In this study, human ADSCs were cultured in 1.1 kPa polyethylene-glycol 3D hydrogels for 10 days with B27, CultureOne (C1), and N2 neural supplements to examine the neural differentiation potential of ADSCs using both chemical and mechanical cues. Following treatment, cell viability, proliferation, morphology, and proteome changes were assessed. Results showed that cell viability was maintained during treatments, and while cells continued to proliferate over time, proliferation slowed down. Morphological changes between 3D untreated cells and treated cells were not observed. However, they were observed among 2D treatments, which exhibited cellular elongation and co-alignment. Proteome analysis showed changes consistent with early neural differentiation for B27 and C1 but not N2. No significant changes were detected using immunocytochemistry, potentially indicating a greater differentiation period was required. In conclusion, treatment of 3D-cultured ADSCs in PEG-based hydrogels with B27 and C1 further enhances neural marker expression, however, this was not observed using supplementation with N2.

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Phosphoregulation of the septin cytoskeleton in neuronal development and disease

Cited by 11 publications

References 138 publications

Septins function in exocytosis via physical interactions with the exocyst complex in fission yeast cytokinesis

Septins function in exocytosis via physical interactions with the exocyst complex in fission yeast cytokinesis

Nicotine Exposure in a Phencyclidine-Induced Mice Model of Schizophrenia: Sex-Selective Medial Prefrontal Cortex Protein Markers of the Combined Insults in Adolescent Mice

Neural Marker Expression in Adipose-Derived Stem Cells Grown in PEG-Based 3D Matrix Is Enhanced in the Presence of B27 and CultureOne Supplements

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