Septin 9 induces lipid droplets growth by a phosphatidylinositol-5-phosphate and microtubule-dependent mechanism hijacked by HCV

Akil, Abdellah; Peng, Juan; Omrane, Mohyeddine; Gondeau, Claire; Desterke, Christophe; Marin, Mickaël; Tronchère, Hélène; Taveneau, Cyntia; Sar, Sokhavuth; Briolotti, Philippe; Benjelloun, Soumaya; Benjouad, Abdelaziz; Maurel, Patrick; Thiers, Valérie; Bressanelli, Stéphane; Samuel, Didier; Bréchot, Christian; Gassama‐Diagne, Ama

doi:10.1038/ncomms12203

Cited by 69 publications

(100 citation statements)

References 72 publications

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“…In cells infected with Shigella this pool of endosomal PI(5)P impedes EGF receptor degradation (Ramel et al, 2011; Boal et al, 2015). Interestingly, exogenous supply of PI(5)P translocates SEPT9 to lipid droplets and possibly other organelles (Akil et al, 2016; Figure 1G). …”

Section: Septins During Endosomal Sortingmentioning

confidence: 98%

Septins As Modulators of Endo-Lysosomal Membrane Traffic

Song

Russo

Krauß

2016

Front. Cell Dev. Biol.

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Septins constitute a family of GTP-binding proteins, which assemble into non-polar filaments in a nucleotide-dependent manner. These filaments can be recruited to negatively charged membrane surfaces. When associated with membranes septin filaments can act as diffusion barriers, which confine subdomains of distinct biological functions. In addition, they serve scaffolding roles by recruiting cytosolic proteins and other cytoskeletal elements. Septins have been implicated in a large variety of membrane-dependent processes, including cytokinesis, signaling, cell migration, and membrane traffic, and several family members have been implicated in disease. However, surprisingly little is known about the molecular mechanisms underlying their biological functions. This review summarizes evidence in support of regulatory roles of septins during endo-lysosomal sorting, with a particular focus on phosphoinositides, which serve as spatial landmarks guiding septin recruitment to distinct subcellular localizations.

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Section: Septins During Endosomal Sortingmentioning

confidence: 98%

Septins As Modulators of Endo-Lysosomal Membrane Traffic

Song

Russo

Krauß

2016

Front. Cell Dev. Biol.

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“…Septin rod association into filaments would be driven by interactions with the plasma membrane (Bridges et al, 2014). Such interactions involve the binding to membrane-specific phosphoinositides like PIP2 (Zhang et al, 1999), PI4,5bis-phosphate (Bertin et al, 2010) or PI5P (Akil et al, 2016) and the local curvature of the membrane, which can be efficiently discriminated by septin rods (Bridges et al, 2016). …”

Section: Molecular Determinants Of Septin Filament Localizationmentioning

confidence: 99%

Cancer-Related Functions and Subcellular Localizations of Septins

Poüs

Klipfel

Baillet

2016

Front. Cell Dev. Biol.

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Since the initial discovery of septin family GTPases, the understanding of their molecular organization and cellular roles keeps being refined. Septins have been involved in many physiological processes and the misregulation of specific septin gene expression has been implicated in diverse human pathologies, including neurological disorders and cancer. In this minireview, we focus on the importance of the subunit composition and subcellular localization of septins relevant to tumor initiation, progression, and metastasis. We especially underline the importance of septin polymer composition and of their association with the plasma membrane, actin, or microtubules in cell functions involved in cancer and in resistance to cancer therapies. Through their scaffolding role, their function in membrane compartmentalization or through their protective function against protein degradation, septins also emerge as critical organizers of membrane-associated proteins and of signaling pathways implicated in cancer-associated angiogenesis, apoptosis, polarity, migration, proliferation, and in metastasis. Also, the question as to which of the free monomers, hetero-oligomers, or filaments is the functional form of mammalian septins is raised and the control over their spatial and temporal localization is discussed. The increasing amount of crosstalks identified between septins and cellular signaling mediators reinforces the exciting possibility that septins could be new targets in anti-cancer therapies or in therapeutic strategies to limit drug resistance.

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“…Lastly, mysterin/RNF213 is a AAA ATPase with a ubiquitin ligase domain, which is implicated in signaling pathways involved in vascular development that supports cancer growth and metastasis (106,107). Interestingly, mysterin is also involved in the stabilization of lipid droplets, which are regulated by SEPT9 in cells that are infected by the hepatitis C virus (108,109).…”

Section: Functional Clustering Of the Sept9 Proteome Points To Isoformentioning

confidence: 99%

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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Septin 9 induces lipid droplets growth by a phosphatidylinositol-5-phosphate and microtubule-dependent mechanism hijacked by HCV

Cited by 69 publications

References 72 publications

Septins As Modulators of Endo-Lysosomal Membrane Traffic

Septins As Modulators of Endo-Lysosomal Membrane Traffic

Cancer-Related Functions and Subcellular Localizations of Septins

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

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