SEC23B is required for pancreatic acinar cell function in adult mice

Khoriaty, Rami; Vogel, Nancy L.; Hoenerhoff, Mark J.; Sans, Maria Dolors; Zhu, Guojing; Everett, Lesley; Nelson, Bradley; Durairaj, Haritha; McKnight, Brooke N.; Zhang, Bin; Ernst, Stephen A.; Ginsburg, David; Williams, John A.

doi:10.1091/mbc.e17-01-0001

Cited by 25 publications

(29 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent characterizations of mice with genetic deficiency of COPII components have extended these findings to mammalian physiology, revealing a variety of complex phenotypes [8][9][10][11][12][13][14][15][16][17] .…”

Section: Discussionmentioning

confidence: 99%

Murine Surf4 is essential for early embryonic development

Emmer

Lascuna

Kotnik

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Newly synthesized proteins co-translationally inserted into the endoplasmic reticulum (ER) lumen may be recruited into anterograde transport vesicles by their association with specific cargo receptors. We recently identified a role for the cargo receptor SURF4 in facilitating the secretion of PCSK9 in cultured cells. To examine the function of SURF4 in vivo, we used CRISPR/Cas9-mediated gene editing to generate mice with germline loss-of-function mutations in Surf4. Surf4 +/mice exhibited grossly normal appearance, behavior, body weight, fecundity, and organ development and demonstrated no significant alterations in circulating plasma levels of PCSK9, apolipoprotein B, or total cholesterol. Surf4 -/mice exhibit embryonic lethality, with complete loss of all Surf4 -/offspring between embryonic days 3.5 and 9.5. Taken together with the much milder phenotypes of PCSK9 or apolipoprotein B deficiency in mice, these findings imply the existence of additional SURF4 cargoes or functions that are essential for murine early embryonic development.

show abstract

Section: Discussionmentioning

confidence: 99%

Murine Surf4 is essential for early embryonic development

Emmer

Lascuna

Kotnik

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…The two human isoforms of Sec23, Sec23A and Sec23B, are ~85% identical to one another and largely redundant in function. As evidenced by interactome analyses, both isoforms interact with any of the four Sec24 isoforms without any differences in paralog specificity (Khoriaty et al, ; Khoriaty et al, ). Their functional equivalence is supported by the findings that both human Sec23 paralogs are able to complement the function of yeast Sec23p and that the Sec23a‐ coding sequence inserted into the endogenous murine Sec23b locus fully rescues the mortality of Sec23B‐deficient mice (Khoriaty et al, ).…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B subviral envelope particles use the COPII machinery for intracellular transport via selective exploitation of Sec24A and Sec23B

Zeyen

Döring

Stieler

et al. 2020

Cellular Microbiology

View full text Add to dashboard Cite

Hepatitis B virus (HBV) is a leading cause of liver disease. Its success as a human pathogen is related to the immense production of subviral envelope particles (SVPs) contributing to viral persistence by interfering with immune functions. To explore cellular pathways involved in SVP formation and egress, we investigated hostpathogen interactions. Yeast-based proteomics revealed Sec24A, a component of the coat protein complex II (COPII), as an interaction partner of the HBV envelope S domain. To understand how HBV co-opts COPII as a proviral machinery, we studied roles of key Sec proteins in HBV-expressing liver cells. Silencing of Sar1, Sec23, and Sec24, which promote COPII assembly concomitant with cargo loading, strongly diminished endoplasmic reticulum (ER) envelope export and SVP secretion. By analysing Sec paralog specificities, we unexpectedly found that the HBV envelope is a selective interaction partner of Sec24A and Sec23B whose functions could not be substituted by their related isoforms. In support, we found that HBV replication upregulated Sec24A and Sec23B transcription. Furthermore, HBV encountered the Sec24A/Sec23B complex via an interaction that involved the N-terminal half of Sec24A and a di-arginine motif of its S domain, mirroring a novel ER export code.Accordingly, an interference with the COPII/HBV cross-talk might display a tool to effectively inhibit SVP release.

show abstract

“…Identification of the molecular machinery underlying eukaryotic protein secretion has been elucidated by elegant work in model systems including yeast and cultured mammalian cells. Recent characterizations of mice with genetic deficiency of COPII components have extended these findings to mammalian physiology, revealing a variety of complex phenotypes [9][10][11][12][13][14][15][16][17][18]. Comparatively little is known about the physiologic role of mammalian cargo receptors in vivo.…”

Section: Discussionmentioning

confidence: 99%

Murine Surf4 is essential for early embryonic development

et al. 2020

Self Cite

View full text Add to dashboard Cite

Newly synthesized proteins co-translationally inserted into the endoplasmic reticulum (ER) lumen may be recruited into anterograde transport vesicles by their association with specific cargo receptors. We recently identified a role for the cargo receptor SURF4 in facilitating the secretion of PCSK9 in cultured cells. To examine the function of SURF4 in vivo, we used CRISPR/Cas9-mediated gene editing to generate mice with germline loss-of-function mutations in Surf4. Heterozygous Surf4 +/mice exhibit grossly normal appearance, behavior, body weight, fecundity, and organ development, with no significant alterations in circulating plasma levels of PCSK9, apolipoprotein B, or total cholesterol, and a detectable accumulation of intrahepatic apoliprotein B. Homozygous Surf4-/mice exhibit embryonic lethality, with complete loss of all Surf4-/offspring between embryonic days 3.5 and 9.5. In contrast to the milder murine phenotypes associated with deficiency of known SURF4 cargoes, the embryonic lethality of Surf4-/mice implies the existence of additional SURF4 cargoes or functions that are essential for murine early embryonic development.

show abstract

SEC23B is required for pancreatic acinar cell function in adult mice

Abstract: Inactivation of Sec23b exclusively in the pancreatic acinar cells of adult mice results in loss of pancreatic mass, with evidence of cell loss, degeneration of exocrine cells (with smaller-than-normal zymogen granules and ER dilation), ER stress, and increased pancreatic cell apoptosis.

Cited by 25 publications

References 30 publications

Murine Surf4 is essential for early embryonic development

Murine Surf4 is essential for early embryonic development

Hepatitis B subviral envelope particles use the COPII machinery for intracellular transport via selective exploitation of Sec24A and Sec23B

Murine Surf4 is essential for early embryonic development

Contact Info

Product

Resources

About