Meeting report – shining light on septins

Caudron, Fabrice; Yadav, Smita

doi:10.1242/jcs.213702

Cited by 4 publications

(4 citation statements)

References 34 publications

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“…Interestingly, recent studies indicate that SEPT1 is required for the nucleation of microtubules from Golgi membranes, suggesting that SEPT9 and myomegalin could be part of the underlying mechanism (79,80). Strikingly, ninein and STIL (centriolar assembly protein) were identified as SEPT9_i1-specific partners, while ALMS1 was detected with only SEPT9_i5 (Figure 4D).…”

Section: Differential Interactions Of Sept9 Isoforms With Nuclear Cementioning

confidence: 84%

Proteomic profiling of the oncogenic septin 9 reveals isoform-specific interactions in breast cancer cells

Devlin

Perkins

Bowen

et al. 2019

Preprint

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Septins are a family of multimeric GTP-binding proteins, which are abnormally expressed in cancer. Septin 9 (SEPT9) is an essential and ubiquitously expressed septin with multiple isoforms, which have differential expression patterns and effects in breast cancer cells. It is unknown, however, if SEPT9 isoforms associate with different molecular networks and functions. Here, we performed a proteomic screen in MCF-7 breast cancer cells to identify the interactome of GFP-SEPT9 isoforms 1, 4 and 5, which vary significantly in their N-terminal extensions. While all three isoforms associated with SEPT2 and SEPT7, the truncated SEPT9_i4 and SEPT9_i5 interacted with septins of the SEPT6 group more promiscuously than SEPT9_i1, which bound predominately SEPT8. Spatial mapping and functional clustering of non-septin partners showed isoform-specific differences in interactions with proteins of distinct subcellular organelles (e.g., nuclei, centrosomes, cilia) and functions such as cell signaling and ubiquitination. Notably, the interactome of the full length SEPT9_i1 was more enriched in cytoskeletal regulators, while the truncated SEPT9_i4 and SEPT9_i5 exhibited preferential and isoform-specific interactions with nuclear, signaling and ubiquitinating proteins. These data provide evidence for isoform-specific interactions, which arise from truncations in the N-terminal extensions of SEPT9, and point to novel roles in the pathogenesis of breast cancer. L.D. performed experiments, analyzed data, made figures and co-wrote manuscript with E.T.S.; G.P. contributed technically and intellectually to ESI/LC-MS/MS experimentation and softwarebased peptide identification; J.R.B. performed microscopy imaging; C.M. created MCF-7 cell lines and contributed to the manuscript; E.T.S. conceived and directed the project (experiments and analyses), drafted manuscript and edited figures.

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Section: Differential Interactions Of Sept9 Isoforms With Nuclear Cementioning

confidence: 84%

Proteomic profiling of the oncogenic septin 9 reveals isoform-specific interactions in breast cancer cells

Devlin

Perkins

Bowen

et al. 2019

Preprint

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“…Septins are a highly conserved protein family composed of 13 mammalian members which are grouped by sequence similarity into in four clusters wherein members may reciprocally provide functional redundancy. [2][3][4]50 These include SEPT2 (SEPT1-2-4-5), SEPT6 (SEPT6-8-10-11-14), SEPT7, and SEPT9 (SEPT3-9-12). Structurally, Septins contain a nucleotide-binding domain and sequence motifs that interact with the phosphate groups of GTP or ATP.…”

Section: Discussionmentioning

confidence: 99%

“…The Septin proteins are members of the translation factor (TRAFAC) class of P-loop nucleotide-binding family and are functionally related to Ras-like GTPases and kinesin and myosin cytoskeletal motors. 1,2 Septins play key roles in mammalian cell division and cytokinesis and are phylogenetically conserved from yeast to humans. They are involved in cancer, aging, infectious diseases, and reproductive and neurodegenerative disorders.…”

Section: Introductionmentioning

confidence: 99%

“…They are involved in cancer, aging, infectious diseases, and reproductive and neurodegenerative disorders. [2][3][4] The roles of individual Septins in cell division, plasma membrane receptor clustering, apoptosis, and prometastatic cytoskeletal component interactions have been investigated in cancer. 5 Somatic Septin mutations have been implicated in the pathogenesis of infant and early childhood acute myeloid leukemia (AML), specifically as fusion partners of the mixed lineage leukemia (MLL) gene.…”

Section: Introductionmentioning

confidence: 99%

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Congenital X‐linked neutropenia with myelodysplasia and somatic tetraploidy due to a germline mutation in SEPT6

et al. 2021

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Septins play key roles in mammalian cell division and cytokinesis but have not previously been implicated in a germline human disorder. A male infant with severe neutropenia and progressive dysmyelopoiesis with tetraploid myeloid precursors was identified. No known genetic etiologies for neutropenia or bone marrow failure were found. However, nextgeneration sequencing of germline samples from the patient revealed a novel, de novo germline stop-loss mutation in the X-linked gene SEPT6 that resulted in reduced SEPT6 staining in bone marrow granulocyte precursors and megakaryocytes. Patient skin fibroblast-derived induced pluripotent stem cells (iPSCs) produced reduced myeloid colonies, particularly of the granulocyte lineage. CRISPR/Cas9 knock-in of the patient's mutation or complete knock-out of SEPT6 was not tolerated in non-patient-derived iPSCs or human myeloid cell lines, but SEPT6 knock-out was successful in an erythroid cell line and resulting clones revealed a propensity to multinucleation. In silico analysis predicts that the mutated protein hinders the dimerization of SEPT6 coiled-coils in both parallel and antiparallel arrangements, which could in turn impair filament formation. These data demonstrate a critical role for SEPT6 in chromosomal segregation in myeloid progenitors that can account for the unusual predisposition to aneuploidy and dysmyelopoiesis.

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Editorial overview: The molecular and cellular biology of septins

Mostowy

Ewers

2019

Cytoskeleton

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This Septins Special Issue of Cytoskeleton addresses fundamental aspects of septin structure, assembly and function. The group of 18 articles has been inspired by the recent European Molecular Biology Organization (EMBO) Workshop entitled 'Molecular and Cellular Biology of Septins' held in Berlin, Germany, on October 8-11, 2017, furthe r described in a recent meeting report (Caudron and Yadav, 2018).

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Meeting report – shining light on septins

Cited by 4 publications

References 34 publications

Proteomic profiling of the oncogenic septin 9 reveals isoform-specific interactions in breast cancer cells

Proteomic profiling of the oncogenic septin 9 reveals isoform-specific interactions in breast cancer cells

Congenital X‐linked neutropenia with myelodysplasia and somatic tetraploidy due to a germline mutation in SEPT6

Editorial overview: The molecular and cellular biology of septins

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