Functional characterisation of the YIPF protein family in mammalian cells

Kranjc, Tilen; Dempsey, Eugene; Cagney, Gerard; Nakamura, Nobuhiro; Shields, Denis C.; Simpson, Jeremy C.

doi:10.1007/s00418-016-1527-3

Cited by 24 publications

(25 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Confocal imaging showed that YIPF6 localized to the ER and Golgi in mouse hepatocytes, based on colocalization with the ER marker protein calnexin and cis-Golgi matrix protein GM130 (SI Appendix, Fig. S5B), consistent with previous reports (37,38). We studied ER and Golgi fractions to determine the subcellular distribution of FGF21.…”

Section: Increased Hepatic Secretion Of Fgf21 Mediates Protective Effsupporting

confidence: 85%

YIPF6 controls sorting of FGF21 into COPII vesicles and promotes obesity

Mazagova

Pan

Yang

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates glucose, lipid, and energy homeostasis. While gene expression of FGF21 is regulated by the nuclear hormone receptor peroxisome proliferator-activated receptor alpha in the fasted state, little is known about the regulation of trafficking and secretion of FGF21. We show that mice with a mutation in the Yip1 domain family, member 6 gene (Klein–Zschocher [KLZ]; Yipf6KLZ/Y) on a high-fat diet (HFD) have higher plasma levels of FGF21 than mice that do not carry this mutation (controls) and hepatocytes from Yipf6KLZ/Y mice secrete more FGF21 than hepatocytes from wild-type mice. Consequently, Yipf6KLZ/Y mice are resistant to HFD-induced features of the metabolic syndrome and have increased lipolysis, energy expenditure, and thermogenesis, with an increase in core body temperature. Yipf6KLZ/Y mice with hepatocyte-specific deletion of FGF21 were no longer protected from diet-induced obesity. We show that YIPF6 binds FGF21 in the endoplasmic reticulum to limit its secretion and specifies packaging of FGF21 into coat protein complex II (COPII) vesicles during development of obesity in mice. Levels of YIPF6 protein in human liver correlate with hepatic steatosis and correlate inversely with levels of FGF21 in serum from patients with nonalcoholic fatty liver disease (NAFLD). YIPF6 is therefore a newly identified regulator of FGF21 secretion during development of obesity and could be a target for treatment of obesity and NAFLD.

show abstract

Section: Increased Hepatic Secretion Of Fgf21 Mediates Protective Effsupporting

confidence: 85%

YIPF6 controls sorting of FGF21 into COPII vesicles and promotes obesity

Mazagova

Pan

Yang

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…YIPF5 is a 5-span transmembrane protein ( Figure 1B) that cycles between the ER and the Golgi and localizes at ER exit sites, the ER-Golgi intermediate compartment, and part of the cis-Golgi (30)(31)(32)(33). Previous studies in HeLa cells have suggested that YIPF5 plays a role in cargo exit from the ER (34), resulting in protein overload, thereby triggering the ER stress response.…”

Section: The Journal Of Clinical Investigation R E S E a R C H A R T mentioning

confidence: 98%

YIPF5 mutations cause neonatal diabetes and microcephaly through endoplasmic reticulum stress

Franco

Lytrivi

Ibrahim

et al. 2020

Journal of Clinical Investigation

View full text Add to dashboard Cite

Neonatal diabetes is caused by single gene mutations reducing pancreatic β cell number or impairing β cell function. Understanding the genetic basis of rare diabetes subtypes highlights fundamental biological processes in β cells. We identified 6 patients from 5 families with homozygous mutations in the YIPF5 gene, which is involved in trafficking between the endoplasmic reticulum (ER) and the Golgi. All patients had neonatal/early-onset diabetes, severe microcephaly, and epilepsy. YIPF5 is expressed during human brain development, in adult brain and pancreatic islets. We used 3 human β cell models ( YIPF5 silencing in EndoC-βH1 cells, YIPF5 knockout and mutation knockin in embryonic stem cells, and patient-derived induced pluripotent stem cells) to investigate the mechanism through which YIPF5 loss of function affects β cells. Loss of YIPF5 function in stem cell–derived islet cells resulted in proinsulin retention in the ER, marked ER stress, and β cell failure. Partial YIPF5 silencing in EndoC-βH1 cells and a patient mutation in stem cells increased the β cell sensitivity to ER stress–induced apoptosis. We report recessive YIPF5 mutations as the genetic cause of a congenital syndrome of microcephaly, epilepsy, and neonatal/early-onset diabetes, highlighting a critical role of YIPF5 in β cells and neurons. We believe this is the first report of mutations disrupting the ER-to-Golgi trafficking, resulting in diabetes.

show abstract

“…cells. YIPF2 belongs to YIP family which has been reported to interact with RAB small G protein and plays vital roles in intracellular vesicular transport 20,22,24,31,37 . Numerous reports have discovered that some chemotherapeutic agents including PEM can induce endoplasmic reticulum (ER) stress in tumor cells 12,38 .…”

Section: Discussionmentioning

confidence: 99%

“…YIPF2 belongs to the YIP protein family, which has been reported to bind to RAB proteins to regulate vesicular transport 22,31 . Thus, we performed co-immunoprecipitation (co-IP) assays to investigate why YIPF2 increased the surface expression of TNFRSF10B.…”

Section: Yipf2 Inhibits the Interaction Between Tnfrsf10b And Rab8mentioning

confidence: 99%

YIPF2 promotes chemotherapeutic agent-mediated apoptosis via enhancing TNFRSF10B recycling to plasma membrane in non-small cell lung cancer cells

Wang

Guo

et al. 2020

Cell Death Dis

View full text Add to dashboard Cite

Non-small cell lung cancer (NSCLC) is the most common histological type of lung cancer, and the identification of the apoptotic process of NSCLC is vital for its treatment. Usually, both the expression level and the cell surface level of TNFRSF10B (TNF Receptor superfamily member 10B) will increase after treatment with some chemotherapeutic agents, which plays a critical role in the apoptosis induction. However, the exact molecular mechanism underlying TNFRSF10B regulation remains largely elusive. Here, we found that TNFRSF10B, along with a vesicular trafficking regulator protein, YIPF2, were upregulated after treatment with pemetrexed (PEM) in NSCLC cells. Besides, YIPF2 increased the surface level of TNFRF10B, while YIPF2 knockdown inhibited the upregulation of TNFRSF10B and its recycling to plasma membrane. In addition, RAB8 decreased the cell surface TNFRSF10B by promoting its removing from plasma membrane to cytoplasm. Furthermore, we found that YIPF2, RAB8 and TNFRSF10B proteins interacted physically with each other. YIPF2 could further inhibit the physical interaction between TNFRSF10B and RAB8, thereby suppressing the removing of TNFRSF10B from plasma membrane to cytoplasm mediated by RAB8 and maintaining its high level on cell surface. Finally, using bioinformatics database, the YIPF2-TNFRSF10B axis was confirmed to be associated with the malignant progression of lung cancer. Taken together, we show that YIPF2 promotes chemotherapeutic agentmediated apoptosis via enhancing TNFRSF10B recycling to plasma membrane in NSCLC cells. These findings may be beneficial for the development of potential prognostic markers of NSCLC and may provide effective treatment strategy.

show abstract

Functional characterisation of the YIPF protein family in mammalian cells

Cited by 24 publications

References 42 publications

YIPF6 controls sorting of FGF21 into COPII vesicles and promotes obesity

YIPF6 controls sorting of FGF21 into COPII vesicles and promotes obesity

YIPF5 mutations cause neonatal diabetes and microcephaly through endoplasmic reticulum stress

YIPF2 promotes chemotherapeutic agent-mediated apoptosis via enhancing TNFRSF10B recycling to plasma membrane in non-small cell lung cancer cells

Contact Info

Product

Resources

About