SNARE protein SEC22B regulates early embryonic development

Wu, S. Julia; Khoriaty, Rami; Kim, Stephanie H.; O’Shea, K. Sue; Zhu, Guojing; Hoenerhoff, Mark J.; Zajac, Cynthia; Oravecz-Wilson, Katherine; Toubai, Tomomi; Sun, Yaping; Ginsburg, David; Reddy, Pavan

doi:10.1038/s41598-019-46536-7

Cited by 9 publications

(9 citation statements)

References 33 publications

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“…Notably, their absence hinders phagosome maturation and Ag cross-presentation (10,11), which translates into phenotypes such as impaired bacterial and tumor clearance (1214). Moreover, a pan-mouse knockout of Sec22b is embryonically lethal (15), highlighting the key importance of this ERGIC-resident SNARE in immunity and development.…”

Section: Sec22b Regulates Inflammatory Responses By Controlling the N...mentioning

confidence: 99%

Sec22b Regulates Inflammatory Responses by Controlling the Nuclear Translocation of NF-κB and the Secretion of Inflammatory Mediators

Duque

Dion

Matte

et al. 2021

The Journal of Immunology

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Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) regulate the vesicle transport machinery in phagocytic cells. Within the secretory pathway, Sec22b is an endoplasmic reticulum–Golgi intermediate compartment (ERGIC)-resident SNARE that controls phagosome maturation and function in macrophages and dendritic cells. The secretory pathway controls the release of cytokines and may also impact the secretion of NO, which is synthesized by the Golgi-active inducible NO synthase (iNOS). Whether ERGIC SNARE Sec22b controls NO and cytokine secretion is unknown. Using murine bone marrow-derived dendritic cells, we demonstrated that inducible NO synthase colocalizes with ERGIC/Golgi markers, notably Sec22b and its partner syntaxin 5, in the cytoplasm and at the phagosome. Pharmacological blockade of the secretory pathway hindered NO and cytokine release, and inhibited NF-κB translocation to the nucleus. Importantly, RNA interference–mediated silencing of Sec22b revealed that NO and cytokine production were abrogated at the protein and mRNA levels. This correlated with reduced nuclear translocation of NF-κB. We also found that Sec22b co-occurs with NF-κB in both the cytoplasm and nucleus, pointing to a role for this SNARE in the shuttling of NF-κB. Collectively, our data unveiled a novel function for the ERGIC/Golgi, and its resident SNARE Sec22b, in the production and release of inflammatory mediators.

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Section: Sec22b Regulates Inflammatory Responses By Controlling the N...mentioning

confidence: 99%

Sec22b Regulates Inflammatory Responses by Controlling the Nuclear Translocation of NF-κB and the Secretion of Inflammatory Mediators

Duque

Dion

Matte

et al. 2021

The Journal of Immunology

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“…A plethora of recent biological studies have been conducted to predict the functions of different SNARE proteins. Gao et al 18 explored the role of SNARE Ykt6 in membrane fusion during autophagy in yeast cells 19 and demonstrated the importance of SNARE Sec. 22b in embryonic development, as lacking this protein can lead to uterus death in experimented mice.…”

Section: Introductionmentioning

confidence: 99%

Identifying SNARE Proteins Using an Alignment-Free Method Based on Multiscan Convolutional Neural Network and PSSM Profiles

Kha

2022

J. Chem. Inf. Model.

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Background: SNARE proteins play a vital role in membrane fusion and cellular physiology and pathological processes. Many potential therapeutics for mental diseases or even cancer based on SNAREs are also developed. Therefore, there is a dire need to predict the SNAREs for further manipulation of these essential proteins, which demands new and efficient approaches. Methods: Some computational frameworks were proposed to tackle the hurdles of biological methods, which take plenty of time and budget to conduct the identification of SNAREs. However, the performances of existing frameworks were insufficiently satisfied, as they failed to retain the SNARE sequence order and capture the mass hidden features from SNAREs. This paper proposed a novel model constructed on the multiscan convolutional neural network (CNN) and position-specific scoring matrix (PSSM) profiles to address these limitations. We employed and trained our model on the benchmark dataset with fivefold cross-validation and two different independent datasets. Results: Overall, the multiscan CNN was cross-validated on the training set and excelled in the SNARE classification reaching 0.963 in AUC and 0.955 in AUPRC. On top of that, with the sensitivity, specificity, accuracy, and MCC of 0.842, 0.968, 0.955, and 0.767, respectively, our proposed framework outperformed previous models in the SNARE recognition task. Conclusions: It is truly believed that our model can contribute to the discrimination of SNARE proteins and general proteins.

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“…51 SEC22B is also required for plasma membrane expansion during neuronal development, 44 autophagosome biogenesis, 57 secretory autophagy, 58 very low-density lipoprotein secretion, 59 and early embryonic murine development. 60 SEC22B has been shown to interact with VPS33B, 31,41 but the precise intracellular localization of this interaction has not been explored. SEC22B has been localized to the ER-Golgi intermediate cellular compartment 51,56 ; however, SEC22B is not restricted to this ER compartment.…”

Section: Discussionmentioning

confidence: 99%

The endoplasmic reticulum protein SEC22B interacts with NBEAL2 and is required for megakaryocyte α-granule biogenesis

Pluthero

et al. 2020

Blood

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Studies of inherited platelet disorders have provided many insights into platelet development and function. Loss of function of neurobeachin-like 2 (NBEAL2) causes Gray Platelet Syndrome (GPS), where the absence of platelet α-granules indicates NBEAL2 is required for their production by precursor megakaryocytes. The endoplasmic reticulum is a dynamic network that interacts with numerous intracellular vesicles and organelles and plays key roles in their development. The megakaryocyte endoplasmic reticulum is very extensive, and in this study we investigated its role in the biogenesis of α-granules by focusing on the membrane-resident trafficking protein SEC22B. Co-immunoprecipitation experiments using tagged proteins expressed in human HEK293 and megakaryocytic imMKCL cells established binding of NBEAL2 with SEC22B, and demonstrated that NBEAL2 can simultaneously bind SEC22B and P-selectin. NBEAL2-SEC22B binding was also observed for endogenous proteins in human megakaryocytes using co-immunoprecipitation, and immunofluorescence microscopy detected substantial overlap. SEC22B binding was localized to a region of NBEAL2 spanning amino acids 1798-1903, where two GPS-associated missense variants have been reported: E1833K and R1839C. NBEAL2 containing either variant did not bind SEC22B co-expressed in HEK292 cells. CRISPR/Cas9 mediated knockout of SEC22B in imMKCL cells resulted in decreased NBEAL2, but not vice versa. Loss of either SEC22B or NBEAL2 expression also resulted in failure of α-granule production and reduced granule proteins in imMKCL cells. We conclude that SEC22B is required for α-granule biogenesis in megakaryocytes, and that interactions with SEC22B and P-selectin facilitate the essential role of NBEAL2 in granule development and cargo stability.

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SNARE protein SEC22B regulates early embryonic development

Cited by 9 publications

References 33 publications

Sec22b Regulates Inflammatory Responses by Controlling the Nuclear Translocation of NF-κB and the Secretion of Inflammatory Mediators

Sec22b Regulates Inflammatory Responses by Controlling the Nuclear Translocation of NF-κB and the Secretion of Inflammatory Mediators

Identifying SNARE Proteins Using an Alignment-Free Method Based on Multiscan Convolutional Neural Network and PSSM Profiles

The endoplasmic reticulum protein SEC22B interacts with NBEAL2 and is required for megakaryocyte α-granule biogenesis

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