The immunoglobulin‐like superfamily member IGSF3 is a developmentally regulated protein that controls neuronal morphogenesis

Usardi, Alessia; Iyer, Keerthana; Sigoillot, Séverine M.; Dusonchet, Antoine; Selimi, Fekrije

doi:10.1002/dneu.22412

Cited by 40 publications

(33 citation statements)

References 77 publications

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“…Lesion-induced reformation of synapses caused IgSF8 to reappear in terminals, whereas blocking olfactory activity prevented the disappearance of IgSF8 from mature synapses 106 . Similarly, the EWI-subfamily member IgSF3 transiently localizes to developing cerebellar GC axon terminals 107 . The localization of IgSF8 to the MF bouton and filopodia suggested a functional requirement for IgSF8 at both sites.…”

Section: Discussionmentioning

confidence: 99%

Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer

et al. 2020

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Excitatory and inhibitory neurons are connected into microcircuits that generate circuit output. Central in the hippocampal CA3 microcircuit is the mossy fiber (MF) synapse, which provides powerful direct excitatory input and indirect feedforward inhibition to CA3 pyramidal neurons. Here, we dissect its cell-surface protein (CSP) composition to discover novel regulators of MF synaptic connectivity. Proteomic profiling of isolated MF synaptosomes uncovers a rich CSP composition, including many CSPs without synaptic function and several that are uncharacterized. Cell-surface interactome screening identifies IgSF8 as a neuronal receptor enriched in the MF pathway. Presynaptic Igsf8 deletion impairs MF synaptic architecture and robustly decreases the density of bouton filopodia that provide feedforward inhibition. Consequently, IgSF8 loss impairs excitation/inhibition balance and increases excitability of CA3 pyramidal neurons. Our results provide insight into the CSP landscape and interactome of a specific excitatory synapse and reveal IgSF8 as a critical regulator of CA3 microcircuit connectivity and function.

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Section: Discussionmentioning

confidence: 99%

Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer

et al. 2020

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“…Other published functions are HIV-1 entry regulation (e.g., CD63 regulates CXCR4 HIV co-receptor expression on cell surface), reverse transcription (e.g., CD81 regulates SAMHD1 turnover), assembly and trans-infection (Suárez et al, 2018). TSPAN7, in addition to its recently discovered role in control of HIV transfer through regulation of actin nucleation (Ménager and Littman, 2016), has been found to be mutated in some forms of X-linked intellectual disabilities, which may be explained by the role of this protein in neuronal morphogenesis (Bassani et al, 2012;Usardi et al, 2017). Indeed, TSPAN7 regulates dendritic spines and filopodia formation in neurons and promotes axonal branching (Bassani et al, 2012;Usardi et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…TSPAN7, in addition to its recently discovered role in control of HIV transfer through regulation of actin nucleation (Ménager and Littman, 2016), has been found to be mutated in some forms of X-linked intellectual disabilities, which may be explained by the role of this protein in neuronal morphogenesis (Bassani et al, 2012;Usardi et al, 2017). Indeed, TSPAN7 regulates dendritic spines and filopodia formation in neurons and promotes axonal branching (Bassani et al, 2012;Usardi et al, 2017). This protein is also believed to play a role in cancer as it promotes migration and proliferation of lung cancer cells and limits myeloma tumor development (Cheong et al, 2015;Wang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Dendritic Cell Maturation Regulates TSPAN7 Function in HIV-1 Transfer to CD4+ T Lymphocytes

Pérot

García-Paredes

Luka

et al. 2020

Front. Cell. Infect. Microbiol.

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Dendritic cells (DCs) serve a key function in host defense, linking innate detection of microbes to activation of pathogen-specific adaptive immune responses. DCs express cell surface receptors for HIV-1 entry, but are relatively resistant to productive viral replication. They do, however, facilitate infection of co-cultured T-helper cells through a process referred to as trans-infection. We previously showed that tetraspanin 7 (TSPAN7), a transmembrane protein, is involved, through positive regulation of actin nucleation, in the transfer of HIV-1 from the dendrites of immature monocyte-derived DCs (iMDDCs) to activated CD4 + T lymphocytes. Various molecular mechanisms have been described regarding HIV-1 trans-infection and seem to depend on DC maturation status. We sought to investigate the crosstalk between DC maturation status, TSPAN7 expression and trans-infection. We followed trans-infection through co-culture of iMDDCs with CD4 + T lymphocytes, in the presence of CXCR4-tropic replicative-competent HIV-1 expressing GFP. T cell infection, DC maturation status and dendrite morphogenesis were assessed through time both by flow cytometry and confocal microscopy. Our previously described TSPAN7/actin nucleation-dependent mechanism of HIV-1 transfer appeared to be mostly observed during the first 20 h of co-culture experiments and to be independent of HIV replication. In the course of co-culture experiments, we observed a progressive maturation of MDDCs, correlated with a decrease in TSPAN7 expression, a drastic loss of dendrites and a change in the shape of DCs. A TSPAN7 and actin nucleation-independent mechanism of transinfection, relying on HIV-1 replication, was then at play. We discovered that TSPAN7 expression is downregulated in response to different innate immune stimuli driving DC maturation, explaining the requirement for a TSPAN7/actin nucleation-independent mechanism of HIV transfer from mature MDDCs (mMDDCs) to T lymphocytes. As previously described, this mechanism relies on the capture of HIV-1 by the I-type lectin CD169/Siglec-1 on mMDDCs and the formation of a "big invaginated pocket" at the surface of DCs, both events being tightly regulated by DC maturation. Interestingly, in iMDDCs, although CD169/Siglec-1 can capture HIV-1, this capture does not lead to HIV-1 transfer to T lymphocytes.

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“…TSPAN7 is a member of the transmembrane 4 superfamily, also called the tetraspanin family, which includes proteins characterized by four transmembrane domains, with one short and one large extracellular loop (20). Previous studies have found that in cerebellar granule cells, TSPAN7 promotes axonal branching, and the size of TSPAN7 clusters is increased by downregulation of IGSF3 expression, which might be at the center of a new signaling pathway controlling brain development (21). In oral tongue squamous cell carcinoma, differential methylation of TSPAN7 was found to be predictive of certain clinical and epidemiologic parameters (22).…”

Section: Discussionmentioning

confidence: 99%

TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT Pathway

Pang

et al. 2021

Front. Oncol.

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The tetraspanin protein superfamily participate in the dynamic regulation of cellular membrane compartments expressed in a variety of tumor types, which may alter the biological properties of cancer cells such as cell development, activation, growth and motility. The role of tetraspanin 7 (TSPAN7) has never been investigated in bladder cancer (BCa). In this study, we aimed to investigate the biological function of TSPAN7 and its therapeutic potential in human BCa. First, via reverse transcription and quantitative real-time PCR (qRT-PCR), we observed downregulation of TSPAN7 in BCa tissues samples and cell lines and found that this downregulation was associated with a relatively high tumor stage and tumor grade. Low expression of TSPAN7 was significantly correlated with a much poorer prognosis for BCa patients than was high expression. Immunohistochemistry (IHC) showed that low TSPAN7 expression was a high-risk predictor of BCa patient overall survival. Furthermore, the inhibitory effects of TSPAN7 on the proliferation and migration of BCa cell lines were detected by CCK-8, wound-healing, colony formation and transwell assays in vitro. Flow cytometry analysis revealed that TSPAN7 induced BCa cell lines apoptosis and cell cycle arrest. In vivo, tumor growth in nude mice bearing tumor xenografts could be obviously affected by overexpression of TSPAN7. Western blotting showed that overexpression of TSPAN7 activated Bax, cleaved caspase-3 and PTEN but inactivated Bcl-2, p-PI3K, and p-AKT to inhibit BCa cell growth via the PTEN/PI3K/AKT pathway. Taken together, our study will help identify a potential marker for BCa diagnosis and supply a target molecule for BCa treatment.

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The immunoglobulin‐like superfamily member IGSF3 is a developmentally regulated protein that controls neuronal morphogenesis

Cited by 40 publications

References 77 publications

Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer

Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer

Dendritic Cell Maturation Regulates TSPAN7 Function in HIV-1 Transfer to CD4+ T Lymphocytes

TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT Pathway

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