Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P11021 (BiP)
 2,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plant HVA22 is a unique abscisic acid (ABA)/stress-induced protein first isolated from barley (Hordeum vulgare) aleurone cells. Its yeast homolog, Yop1p, functions in vesicular trafficking and in the endoplasmic reticulum (ER) network in vivo. To examine the roles of plant HVA22, barley HVA22 was ectopically expressed in barley aleurone cells. Overexpression of HVA22 proteins inhibited gibberellin (GA)-induced formation of large digestive vacuoles, which is an important aspect of GA-induced programmed cell death in aleurone cells. The effect of HVA22 was specific, because overexpression of green fluorescent protein or another ABA-induced protein, HVA1, did not lead to the same effect. HVA22 acts downstream of the transcription factor GAMyb, which activates programmed cell death and other GA-mediated processes. Moreover, expression of HVA22:green fluorescent protein fusion proteins showed network and punctate fluorescence patterns, which were colocalized with an ER marker, BiP:RFP, and a Golgi marker, ST:mRFP, respectively. In particular, the transmembrane domain 2 was critical for protein localization and stability. Ectopic expression of the most phylogenetically similar Arabidopsis (Arabidopsis thaliana) homolog, AtHVA22D, also resulted in the inhibition of vacuolation to a similar level as HVA22, indicating function conservation between barley HVA22 and some Arabidopsis homologs. Taken together, we show that HVA22 is an ER- and Golgi-localized protein capable of negatively regulating GA-mediated vacuolation/programmed cell death in barley aleurone cells. We propose that ABA induces the accumulation of HVA22 proteins to inhibit vesicular trafficking involved in nutrient mobilization to delay coalescence of protein storage vacuoles as part of its role in regulating seed germination and seedling growth.
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PMID:An abscisic acid-induced protein, HVA22, inhibits gibberellin-mediated programmed cell death in cereal aleurone cells. 1858 33

Arginine-vasopressin (AVP) is a peptide hormone normally secreted from neuroendocrine cells via the regulated secretory pathway. In Familial Neurohypophyseal Diabetes Insipidus (FNDI), an autosomal dominant form of central diabetes insipidus, mutations of pro-vasopressin appear to accumulate in the endoplasmic reticulum (ER) causing a lack of biologically active AVP in the blood. To investigate the effect of pro-vasopressin mutations regarding intracellular functions of protein targeting and secretion, we created two FNDI-associated amino acid substitution mutants, e.g., G14R, and G17V in frame with green fluorescent protein (GFP) and pro-vasopressin (VP) in frame with red fluorescent protein (VP-RFP). Fluorescence microscopy of Neuro-2a cells expressing these constructs revealed co-localization of VP-GFP and VP-RFP to punctate granules along the length and accumulating at the tips of neurites, characteristic of regulated secretory granules. In contrast, the two FNDI-associated amino acid substitution mutants, e.g., G14R-GFP, and G17VGFP, were localized to a perinuclear region of the Neuro-2a cells characteristic of the endoplasmic reticulum. Co-expression of these mutants with VP-RFP showed VP-RFP was retained in the ER, co-localized with the mutants suggesting the formation of heterodimers as found in FNDI. Stimulated secretion experiments indicated that VP-GFP was secreted in an inducible manner whereas, G14R-GFP and G17V-GFP were retained to nearly 100% within the cells. Analysis by western blotting and semi-quantitative RT-PCR indicated an increased protein and mRNA expression for an ER resident molecular chaperone, BiP. Further analysis of ER-storage disease-associated proteins such as caspase 12 and CHOP showed an increase in these as well. The results suggest that G14R-GFP and G17V-GFP are retained in the ER of Neuro-2a cells, resulting in up-regulation of the molecular chaperone BiP, and activation of the ER-storage disease-associated caspase cascade system.
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PMID:Misfolding of Mutated Vasopressin Causes ER-Retention and Activation of ER-Stress Markers in Neuro-2a Cells. 2456 68

Alternative splicing (AS) is an important molecular mechanism by which single genes can generate multiple mRNA isoforms. We reported previously that, in Oryza sativa, the cyclophilin 19-4 (OsCYP19-4.1) transcript was significantly upregulated in response to cold stress, and that transgenic plants were cold tolerant. Here we show that, under cold stress, OsCYP19-4 produces eight transcript variants by intron retention and exon skipping, resulting in production of four distinct protein isoforms. The OsCYP19-4 AS isoforms exhibited different cellular localizations in the epidermal cells: in contrast to OsCYP19-4.1, the OsCYP19-4.2 and OsCYP19-4.3 proteins were primarily targeted to guard and subsidiary cells, whereas OsCYP19-4.5, which consists largely of an endoplasmic reticulum (ER) targeting signal, was co-localized with the RFP-BiP marker in the ER. In OsCYP19-4.2, the key residues of the PPIase domain are altered; consistent with this, recombinant OsCYP19-4.2 had significantly lower PPIase activity than OsCYP19-4.1 in vitro. Specific protein-protein interactions between OsCYP19-4.2/3 and AtRCN1 were verified in yeast two-hybrid (Y2H) and bimolecular fluoresence complementation (BiFC assays), although the OsCYP19-4 isoforms could not bind each other. Based on these results, we propose that two OsCYP19-4 AS isoforms, OsCYP19-4.2 and OsCYP19-4.3, play roles linking auxin transport and cold stress via interactions with RCN1.
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PMID:The OsCYP19-4 Gene Is Expressed as Multiple Alternatively Spliced Transcripts Encoding Isoforms with Distinct Cellular Localizations and PPIase Activities under Cold Stress. 2744 7