Assays for Autophagy III: Observing Dynamic Protein Trafficking

Unliganded steroid receptors are assembled into heterocomplexes with heat-shock protein (hsp) 90 by a multiprotein chaperone machinery. In addition to binding the receptors at the chaperone site, hsp90 binds cofactors at other sites that are part of the assembly machinery, as well as immunophilins that connect the assembled receptor-hsp90 heterocomplexes to a protein trafficking pathway. The hsp90-/hsp70-based chaperone machinery interacts with the unliganded glucocorticoid receptor to open the steroid-binding cleft to access by a steroid, and the machinery interacts in very dynamic fashion with the liganded, transformed receptor to facilitate its translocation along microtubular highways to the nucleus. In the nucleus, the chaperone machinery interacts with the receptor in transcriptional regulatory complexes after hormone dissociation to release the receptor and terminate transcriptional activation. By forming heterocomplexes with hsp90, the chaperone machinery stabilizes the receptor to degradation by the ubiquitin-proteasome pathway of proteolysis.

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Protein trafficking: Glycan structure sorts it out

Functional Glycomics ◽

10.1038/fg.2009.33 ◽

2009 ◽

Author(s):

Catherine Goodman

Keyword(s):

Protein Trafficking ◽

Glycan Structure

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Faculty Opinions recommendation of Genetic variation in Mon1a affects protein trafficking and modifies macrophage iron loading in mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1090446.543708 ◽

2007 ◽

Author(s):

Caroline Philpott

Keyword(s):

Genetic Variation ◽

Protein Trafficking ◽

Iron Loading

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Therapeutic Approaches to Alzheimer’s Type of Dementia: A Focus on FGF21 Mediated Neuroprotection

Current Pharmaceutical Design ◽

10.2174/1381612825666190716101411 ◽

2019 ◽

Vol 25 (23) ◽

pp. 2555-2568 ◽

Cited By ~ 5

Author(s):

Rajeev Taliyan ◽

Sarathlal K. Chandran ◽

Violina Kakoty

Keyword(s):

Diabetes Mellitus ◽

Protein Trafficking ◽

Metabolic Stress ◽

Insulin Receptors ◽

Metabolic Dysfunction ◽

Beneficial Effects ◽

Glucose And Lipid Metabolism ◽

Endocrine Hormone ◽

Metabolic Conditions ◽

The Brain

Neurodegenerative disorders are the most devastating disorder of the nervous system. The pathological basis of neurodegeneration is linked with dysfunctional protein trafficking, mitochondrial stress, environmental factors and aging. With the identification of insulin and insulin receptors in some parts of the brain, it has become evident that certain metabolic conditions associated with insulin dysfunction like Type 2 diabetes mellitus (T2DM), dyslipidemia, obesity etc., are also known to contribute to neurodegeneration mainly Alzheimer’s Disease (AD). Recently, a member of the fibroblast growth factor (FGF) superfamily, FGF21 has proved tremendous efficacy in diseases like diabetes mellitus, obesity and insulin resistance (IR). Increased levels of FGF21 have been reported to exert multiple beneficial effects in metabolic syndrome. FGF21 receptors are present in certain areas of the brain involved in learning and memory. However, despite extensive research, its function as a neuroprotectant in AD remains elusive. FGF21 is a circulating endocrine hormone which is mainly secreted by the liver primarily in fasting conditions. FGF21 exerts its effects after binding to FGFR1 and co-receptor, β-klotho (KLB). It is involved in regulating energy via glucose and lipid metabolism. It is believed that aberrant FGF21 signalling might account for various anomalies like neurodegeneration, cancer, metabolic dysfunction etc. Hence, this review will majorly focus on FGF21 role as a neuroprotectant and potential metabolic regulator. Moreover, we will also review its potential as an emerging candidate for combating metabolic stress induced neurodegenerative abnormalities.

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Molecular basis of ciliary defects caused by compound heterozygous IFT144/WDR19 mutations found in cranioectodermal dysplasia

Human Molecular Genetics ◽

10.1093/hmg/ddab034 ◽

2021 ◽

Author(s):

Yamato Ishida ◽

Takuya Kobayashi ◽

Shuhei Chiba ◽

Yohei Katoh ◽

Kazuhisa Nakayama

Keyword(s):

Protein Trafficking ◽

Primary Cilia ◽

Intraflagellar Transport ◽

Missense Variant ◽

Cellular Level ◽

Compound Heterozygous ◽

Hypomorphic Allele ◽

Genes Encoding ◽

Specific Proteins ◽

Compound Heterozygous Mutations

Abstract Primary cilia contain specific proteins to achieve their functions as cellular antennae. Ciliary protein trafficking is mediated by the intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B complexes. Mutations in genes encoding the IFT-A subunits (IFT43, IFT121/WDR35, IFT122, IFT139/TTC21B, IFT140, and IFT144/WDR19) often result in skeletal ciliopathies, including cranioectodermal dysplasia (CED). We here characterized the molecular and cellular defects of CED caused by compound heterozygous mutations in IFT144 [the missense variant IFT144(L710S) and the nonsense variant IFT144(R1103*)]. These two variants were distinct with regard to their interactions with other IFT-A subunits and with the IFT-B complex. When exogenously expressed in IFT144-knockout (KO) cells, IFT144(L710S) as well as IFT144(WT) rescued both moderately compromised ciliogenesis and the abnormal localization of ciliary proteins. As the homozygous IFT144(L710S) mutation was found to cause autosomal recessive retinitis pigmentosa, IFT144(L710S) is likely to be hypomorphic at the cellular level. In striking contrast, the exogenous expression of IFT144(R1103*) in IFT144-KO cells exacerbated the ciliogenesis defects. The expression of IFT144(R1103*) together with IFT144(WT) restored the abnormal phenotypes of IFT144-KO cells. However, the coexpression of IFT144(R1103*) with the hypomorphic IFT144(L710S) variant in IFT144-KO cells, which mimics the genotype of compound heterozygous CED patients, resulted in severe ciliogenesis defects. Taken together, these observations demonstrate that compound heterozygous mutations in IFT144 cause severe ciliary defects via a complicated mechanism, where one allele can cause severe ciliary defects when combined with a hypomorphic allele.

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Regulation of blood-testis barrier dynamics by TGF- 3 is a Cdc42-dependent protein trafficking event

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1001077107 ◽

2010 ◽

Vol 107 (25) ◽

pp. 11399-11404 ◽

Cited By ~ 57

Author(s):

E. W. P. Wong ◽

D. D. Mruk ◽

W. M. Lee ◽

C. Y. Cheng

Keyword(s):

Protein Trafficking ◽

Dependent Protein ◽

Blood Testis Barrier

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Altered cellular localisation and expression, together with unconventional protein trafficking, of prion protein, PrPC, in type 1 diabetes

Diabetologia ◽

10.1007/s00125-021-05501-8 ◽

2021 ◽

Author(s):

Helmut Hiller ◽

Changjun Yang ◽

Dawn E. Beachy ◽

Irina Kusmartseva ◽

Eduardo Candelario-Jalil ◽

...

Keyword(s):

Type 1 Diabetes ◽

Prion Protein ◽

Protein Trafficking ◽

Cellular Localisation

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SNF1-related protein kinase 1: the many-faced signaling hub regulating developmental plasticity in plants

Journal of Experimental Botany ◽

10.1093/jxb/erab079 ◽

2021 ◽

Author(s):

Muhammed Jamsheer K ◽

Manoj Kumar ◽

Vibha Srivastava

Keyword(s):

Protein Kinase ◽

Environmental Conditions ◽

Protein Trafficking ◽

Developmental Plasticity ◽

Inositol Phosphate ◽

Future Research ◽

Primary Metabolism ◽

Related Protein ◽

Comprehensive Overview ◽

Cellular Processes

AbstractThe Snf1-related protein kinase 1 (SnRK1) is the plant homolog of the heterotrimeric AMP-activated protein kinase/sucrose non-fermenting 1 (AMPK/Snf1), which works as a major regulator of growth under nutrient-limiting conditions in eukaryotes. Along with its conserved role as a master regulator of sugar starvation responses, SnRK1 is involved in controlling the developmental plasticity and resilience under diverse environmental conditions in plants. In this review, through mining and analyzing the interactome and phosphoproteome data of SnRK1, we are highlighting its role in fundamental cellular processes such as gene regulation, protein synthesis, primary metabolism, protein trafficking, nutrient homeostasis, and autophagy. Along with the well-characterized molecular interaction in SnRK1 signaling, our analysis highlights several unchartered regions of SnRK1 signaling in plants such as its possible communication with chromatin remodelers, histone modifiers, and inositol phosphate signaling. We also discuss potential reciprocal interactions of SnRK1 signaling with other signaling pathways and cellular processes, which could be involved in maintaining flexibility and homeostasis under different environmental conditions. Overall, this review provides a comprehensive overview of the SnRK1 signaling network in plants and suggests many novel directions for future research.

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Rosa canina L. Can Restore Endoplasmic Reticulum Alterations, Protein Trafficking and Membrane Integrity in a Dextran Sulfate Sodium-Induced Inflammatory Bowel Disease Phenotype

Nutrients ◽

10.3390/nu13020441 ◽

2021 ◽

Vol 13 (2) ◽

pp. 441

Author(s):

Dalanda Wanes ◽

Mohamad Toutounji ◽

Hichem Sebai ◽

Sandra Rizk ◽

Hassan Y. Naim

Keyword(s):

Inflammatory Bowel Disease ◽

Endoplasmic Reticulum ◽

Lipid Rafts ◽

Protein Trafficking ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Membrane Integrity ◽

Membrane Glycoproteins ◽

Rosa Canina ◽

Inflammatory Bowel

Rosa canina L. is a natural polyphenol-rich medicinal plant that exhibits antioxidant and anti-inflammatory activities. Recent in vivo studies have demonstrated that a methanol extract of Rosa canina L. (RCME) has reversed an inflammatory bowel disease (IBD)-like phenotype that has been triggered by dextran sulfate sodium (DSS) in mice. In the current study, we investigated the effects of RCME on perturbations of cellular mechanisms induced by DSS-treatment of intestinal Caco-2 cells, including stress response in the endoplasmic reticulum (ER), protein trafficking and sorting as well as lipid rafts integrity and functional capacities of an intestinal enzyme. 6 days post-confluent cells were treated for 24 h with DSS (3%) or simultaneously with DSS (3%) and RCME (100 µg/mL) or exclusively with RCME (100 µg/mL) or not treated. The results obtained demonstrate the ability of RCME to counteract the substantial increase in the expression levels of several ER stress markers in DSS-treated cells. Concomitantly, the delayed trafficking of intestinal membrane glycoproteins sucrase-isomaltase (SI) and dipeptidyl peptidase 4 (DPP4) induced by DSS between the ER and the Golgi has been compromised by RCME. Furthermore, RCME restored the partially impaired polarized sorting of SI and DPP4 to the brush border membrane. An efficient sorting mechanism of SI and DPP4 is tightly associated with intact lipid rafts structures in the trans-Golgi network (TGN), which have been distorted by DSS and normalized by RCME. Finally, the enzymatic activities of SI are enhanced in the presence of RCME. Altogether, DSS treatment has triggered ER stress, impaired trafficking and function of membrane glycoproteins and distorted lipid rafts, all of which can be compromised by RCME. These findings indicate that the antioxidants in RCME act at two major sites in Caco-2 cells, the ER and the TGN and are thus capable of maintaining the membrane integrity by correcting the sorting of membrane-associated proteins.

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