Syntaxin-4 is implicated in the secretion of antibodies by human plasma cells

Gómez-Jaramillo, Laura; Delgado-Pérez, Luis; Reales, Elena; Mora-López, Francisco; Mateos, Rosa M.; García-Poley, Antonio; Brieva, José A.; Campos‐Caro, Antonio

doi:10.1189/jlb.0113031

Cited by 15 publications

(19 citation statements)

References 40 publications

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“…VAMP8 has also been reported to inhibit phagocytosis by dendritic cells (Ho et al, 2008). Stx3 and Stx4 are mainly plasma membrane localized SNAREs mediating exocytosis, but also have intracellular roles in immune cells (Naegelen et al, 2015; Collins et al, 2014; Stow et al, 2009; Stanley and Lacy, 2010; Lacy and Stow, 2011; Murray and Stow, 2014; Gómez-Jaramillo et al, 2014; Frank et al, 2011). Our FRET-FLIM experiments revealed FRET of fluorescently labeled Stx3 with VAMP3 in live dendritic cells and this was predominantly present at the plasma membrane, indicative of increased Stx3-VAMP3 complexing at this site.…”

Section: Introductionmentioning

confidence: 99%

Fluorescence Lifetime Imaging Microscopy reveals rerouting of SNARE trafficking driving dendritic cell activation

Verboogen

Mancha

Beest

et al. 2017

eLife

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SNARE proteins play a crucial role in intracellular trafficking by catalyzing membrane fusion, but assigning SNAREs to specific intracellular transport routes is challenging with current techniques. We developed a novel Förster resonance energy transfer-fluorescence lifetime imaging microscopy (FRET-FLIM)-based technique allowing visualization of real-time local interactions of fluorescently tagged SNARE proteins in live cells. We used FRET-FLIM to delineate the trafficking steps underlying the release of the inflammatory cytokine interleukin-6 (IL-6) from human blood-derived dendritic cells. We found that activation of dendritic cells by bacterial lipopolysaccharide leads to increased FRET of fluorescently labeled syntaxin 4 with VAMP3 specifically at the plasma membrane, indicating increased SNARE complex formation, whereas FRET with other tested SNAREs was unaltered. Our results revealed that SNARE complexing is a key regulatory step for cytokine production by immune cells and prove the applicability of FRET-FLIM for visualizing SNARE complexes in live cells with subcellular spatial resolution.DOI: http://dx.doi.org/10.7554/eLife.23525.001

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Section: Introductionmentioning

confidence: 99%

Fluorescence Lifetime Imaging Microscopy reveals rerouting of SNARE trafficking driving dendritic cell activation

Verboogen

Mancha

Beest

et al. 2017

eLife

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“…21) and STX4. 22,23 In the present work, we focused on the vesicleassociated R-SNARE proteins implicated in this process. 33 Initially, we noticed that PCs express all VAMP family members, except VAMP1.…”

Section: Discussionmentioning

confidence: 99%

“…Considering that VAMP2 seems to be responsible, at least in part, for Ig secretion by PCs, it was hypothesized that it had to be complexed with other SNAREs, such as SNAP23 21 and/or STX4, 22,23 which are equally involved in the antibody secretion process. To confirm this, we examined whether VAMP2 could interact in situ with STX4 using the proximity ligation assay technique and confocal microscopy.…”

Section: Interaction Between Vamp2 and Stx4 In Human Pcsmentioning

confidence: 99%

“…In contrast, siRNAmediated knockdown of the other VAMP proteins did not show any significant effect. Because siRNA previously demonstrated a reduction in Ig secretion, 22 a specific siRNA for STX4 was used as a positive control. The combination of two VAMP siRNA simultaneously, that is, for VAMP2+VAMP3 or VAMP7 +VAMP8, revealed no differences compared with the single siRNA (not shown).…”

Section: Expression and Cellular Localization Of Vamp Proteins In Hummentioning

confidence: 99%

“…In previous studies, SNAP23 has been identified and characterized as the SNAP-25 family member, and STX, as the syntaxin family member involved in Ig secretion by human PCs; [21][22][23] however, the VAMP family member, that is, the other component necessary to form the SNARE complex, remains to be identified. The aim of the present study was, therefore, to analyze which isoform/s of the VAMP protein/s is/are implicated in Ig secretion by human PCs.…”

Section: Introductionmentioning

confidence: 99%

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VAMP2 is implicated in the secretion of antibodies by human plasma cells and can be replaced by other synaptobrevins

et al. 2016

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The production and secretion of antibodies by human plasma cells (PCs) are two essential processes of humoral immunity. The secretion process relies on a group of proteins known as soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), which are located in the plasma membrane (t-SNAREs) and in the antibody-carrying vesicle membrane (v-SNARE), and mediate the fusion of both membranes. We have previously shown that SNAP23 and STX4 are the t-SNAREs responsible for antibody secretion. Here, using human PCs and antibody-secreting cell lines, we studied and characterized the expression and subcellular distribution of vesicle associated membrane protein (VAMP) isoforms, demonstrating that all isoforms (with the exception of VAMP1) are expressed by the referenced cells. Furthermore, the functional role in antibody secretion of each expressed VAMP isoform was tested using siRNA. Our results show that VAMP2 may be the v-SNARE involved in vesicular antibody release. To further support this conclusion, we used tetanus toxin light chain to cleave VAMP2, conducted experiments to verify co-localization of VAMP2 in antibody-carrying vesicles, and demonstrated the coimmunoprecipitation of VAMP2 with STX4 and SNAP23 and the in situ interaction of VAMP2 with STX4. Taken together, these findings implicate VAMP2 as the main VAMP isoform functionally involved in antibody secretion.

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SNAREs and developmental disorders

Tang

2020

Journal Cellular Physiology

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Members of the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) family mediate membrane fusion processes associated with vesicular trafficking and autophagy. SNAREs mediate core membrane fusion processes essential for all cells, but some SNAREs serve cell/tissue type‐specific exocytic/endocytic functions, and are therefore critical for various aspects of embryonic development. Mutations or variants of their encoding genes could give rise to developmental disorders, such as those affecting the nervous system and immune system in humans. Mutations to components in the canonical synaptic vesicle fusion SNARE complex (VAMP2, STX1A/B, and SNAP25) and a key regulator of SNARE complex formation MUNC18‐1, produce variant phenotypes of autism, intellectual disability, movement disorders, and epilepsy. STX11 and MUNC18‐2 mutations underlie 2 subtypes of familial hemophagocytic lymphohistiocytosis. STX3 mutations contribute to variant microvillus inclusion disease. Chromosomal microdeletions involving STX16 play a role in pseudohypoparathyroidism type IB associated with abnormal imprinting of the GNAS complex locus. In this short review, I discuss these and other SNARE gene mutations and variants that are known to be associated with a variety developmental disorders, with a focus on their underlying cellular and molecular pathological basis deciphered through disease modeling. Possible pathogenic potentials of other SNAREs whose variants could be disease predisposing are also speculated upon.

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Syntaxin-4 is implicated in the secretion of antibodies by human plasma cells

Cited by 15 publications

References 40 publications

Fluorescence Lifetime Imaging Microscopy reveals rerouting of SNARE trafficking driving dendritic cell activation

Fluorescence Lifetime Imaging Microscopy reveals rerouting of SNARE trafficking driving dendritic cell activation

VAMP2 is implicated in the secretion of antibodies by human plasma cells and can be replaced by other synaptobrevins

SNAREs and developmental disorders

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