Autophagy and VMP1 Expression Are Early Cellular Events in Experimental Diabetes

Grasso, Daniel; Sacchetti, Maria Luisa; Bruno, L; Ré, Andrea Lo; lovanna, J; Gonzalez, Claudio; Vaccaro, María I.

doi:10.1159/000178878

Cited by 32 publications

(25 citation statements)

References 33 publications

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“…Here, we show that KRAS, an oncogene that induces autophagy, triggers the activation of VMP1 in vitro and in vivo. VMP1, a transmembrane protein essential for the formation of the autophagosome, plays a role in autophagy during stress responses (13)(14)(15)(16). Genetic screens in Caenorhabditis elegans identified VMP1 as one of three essential components of the metazoan-specific autophagic pathway (34).…”

Section: Discussionmentioning

confidence: 99%

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Novel AKT1-GLI3-VMP1 Pathway Mediates KRAS Oncogene-induced Autophagy in Cancer Cells

Ré

Fernández‐Barrena

Almada

et al. 2012

Journal of Biological Chemistry

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Background: Autophagy plays a role in cancer development. Results: Oncogenic KRAS induces Vacuole Membrane Protein 1 (VMP1) through a novel AKT1-GLI3-p300 pathway and requires VMP1 to regulate autophagy in cancer cells. Conclusion: Define a novel pathway initiated by the oncogene KRAS regulating autophagy. Significance: These findings contribute to the understanding of the mechanism underlying oncogene-induced autophagy.

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Section: Discussionmentioning

confidence: 99%

“…We indentify the transmembrane protein VMP1, 6 a key mediator of autophagy (13)(14)(15)(16)(17), as a transcriptional target of oncogenic KRAS signaling in cancer cells. VMP1 has been identified as one of three essential autophagy genes conserved from worms to mammals.…”

mentioning

confidence: 99%

Novel AKT1-GLI3-VMP1 Pathway Mediates KRAS Oncogene-induced Autophagy in Cancer Cells

Ré

Fernández‐Barrena

Almada

et al. 2012

Journal of Biological Chemistry

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“…Thus, it appears that autophagic deficiency in pancreatic B-cells plays an important role in the pathogenesis of type 2 diabetes. Although various studies have suggested potential molecular mechanisms to describe the pathway surrounding the contribution of autophagy in B-cells and diabetes (Marsh et al 2007, Grasso et al 2009, Masini et al 2009, Las et al 2011, none have been definitively proven or reproduced. As more evidence concerning the general involvement of autophagic deficiency in type 2 diabetes accumulates, its precise delineation will be critical in taking advantage of the discovery.…”

Section: Pancreatic Isletsmentioning

confidence: 99%

Autophagy in the endocrine glands

Weckman¹,

Ieva²,

Rotondo³

et al. 2014

Journal of Molecular Endocrinology

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Autophagy is an important cellular process involving the degradation of intracellular components. Its regulation is complex and while there are many methods available, there is currently no single effective way of detecting and monitoring autophagy. It has several cellular functions that are conserved throughout the body, as well as a variety of different physiological roles depending on the context of its occurrence in the body. Autophagy is also involved in the pathology of a wide range of diseases. Within the endocrine system, autophagy has both its traditional conserved functions and specific functions. In the endocrine glands, autophagy plays a critical role in controlling intracellular hormone levels. In peptide-secreting cells of glands such as the pituitary gland, crinophagy, a specific form of autophagy, targets the secretory granules to control the levels of stored hormone. In steroid-secreting cells of glands such as the testes and adrenal gland, autophagy targets the steroid-producing organelles. The dysregulation of autophagy in the endocrine glands leads to several different endocrine diseases such as diabetes and infertility. This review aims to clarify the known roles of autophagy in the physiology of the endocrine system, as well as in various endocrine diseases.

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“…It has been implicated in an array of cellular processes: organellar biogenesis, endo-, exo-, phagocytosis and protein secretion [2]; apoptosis [1]; adhesion [4]; and, perhaps most notably, macroautophagy (henceforth: "autophagy"; [3]), as well as a special type of autophagy, namely zymophagy, in which zymogen granules—subcellular structures that contain inactive digestive enzyme—are selectively degraded [5]. Last but not least, it has been shown to play a key role in certain human diseases, namely pancreatitis [1,6], diabetes [7], and several types of cancer [4,8,9]. The phenotypes and processes in which VMP1 is involved are gradually being elucidated at the molecular level: its plasma-membrane localization and cell-adhesion capacity, for instance, account for its reduced expression in metastasized cancer cells [4], since loss of adhesion is essensial for metastasis [10]; and its role in zymophagy helps to protect pancreas cells from digesting themselves during pancreatitis [5].…”

Section: Introductionmentioning

confidence: 99%

VMP1-deficient Chlamydomonas exhibits severely aberrant cell morphology and disrupted cytokinesis

et al. 2014

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BackgroundThe versatile Vacuole Membrane Protein 1 (VMP1) has been previously investigated in six species. It has been shown to be essential in macroautophagy, where it takes part in autophagy initiation. In addition, VMP1 has been implicated in organellar biogenesis; endo-, exo- and phagocytosis, and protein secretion; apoptosis; and cell adhesion. These roles underly its proven involvement in pancreatitis, diabetes and cancer in humans.ResultsIn this study we analyzed a VMP1 homologue from the green alga Chlamydomonas reinhardtii. CrVMP1 knockdown lines showed severe phenotypes, mainly affecting cell division as well as the morphology of cells and organelles. We also provide several pieces of evidence for its involvement in macroautophagy.ConclusionOur study adds a novel role to VMP1's repertoire, namely the regulation of cytokinesis. Though the directness of the observed effects and the mechanisms underlying them remain to be defined, the protein's involvement in macroautophagy in Chlamydomonas, as found by us, suggests that CrVMP1 shares molecular characteristics with its animal and protist counterparts.

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Autophagy and VMP1 Expression Are Early Cellular Events in Experimental Diabetes

Cited by 32 publications

References 33 publications

Novel AKT1-GLI3-VMP1 Pathway Mediates KRAS Oncogene-induced Autophagy in Cancer Cells

Novel AKT1-GLI3-VMP1 Pathway Mediates KRAS Oncogene-induced Autophagy in Cancer Cells

Autophagy in the endocrine glands

VMP1-deficient Chlamydomonas exhibits severely aberrant cell morphology and disrupted cytokinesis

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