Ornithine decarboxylase antizyme inhibitor 2 regulates intracellular vesicle trafficking

Kanerva, Kristiina; Mäkitie, Laura; Back, Nathan; Andersson, Leif C.

doi:10.1016/j.yexcr.2010.02.021

Cited by 28 publications

(31 citation statements)

References 51 publications

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“…The cross-linking experiments also support that the AZIN2 monomer may be in close contact with other cellular proteins. These findings are in agreement with previous experiments that showed that AZIN2 is associated to membranes of the Golgi network [39,51]. In addition, the fact that cotransfection with AZ1 prevented the cross-linking of AZIN2 with such membrane proteins, may also be explained by considering that the binding to AZ1 precludes the interaction of AZIN2 with these target proteins, as suggests a preliminary docked model of the AZIN2-AZ1 complex, in which the binding of AZ1 to the AZBE domain may compete with the binding of AZIN2 to the membranes, because the partial overlapping of these two AZIN2 domains (Ramos-Molina et al, unpublished data).…”

Section: Discussionsupporting

confidence: 94%

Structural and degradative aspects of ornithine decarboxylase antizyme inhibitor 2

et al. 2014

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HighlightsAZIN2, unlike ornithine decarboxylase, exists as a monomer in solution.Conserved residues among AZIN2 orthologs are critical for the binding to antizymes (AZs).Substitution of the conserved residues affects the ability of AZIN2 to modulate polyamine levels.AZIN2 and AZs are extremely labile proteins, which mutually stabilize each other.Other proteolytic systems, besides the 26S proteasome, might be involved in AZIN2 degradation.

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Section: Discussionsupporting

confidence: 94%

Structural and degradative aspects of ornithine decarboxylase antizyme inhibitor 2

et al. 2014

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“…This new set of AZIN2 expressing tissues have in common to possess either endocrine or paracrine functions, and therefore, to be endowed with a prominent secretory activity. This fact, together with the reported subcellular localization in the ERGIC [23] and in the trans-Golgi network [24], key components of the secretory pathway, suggests a relevant role for AZIN2 in this process. This contention is also supported by recent findings showing that polyamines may influence the secretory activity in various systems.…”

Section: Discussionmentioning

confidence: 72%

“…Thus, polyamines have been found to be present in mast cell secretory granules where they are important for granule homeostasis [25]. In addition, the depletion of cellular polyamines in different type of cells may affect the intracellular vesicle trafficking [24].…”

Section: Discussionmentioning

confidence: 99%

Antizyme Inhibitor 2 Hypomorphic Mice. New Patterns of Expression in Pancreas and Adrenal Glands Suggest a Role in Secretory Processes

et al. 2013

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The intracellular levels of polyamines, polycations implicated in proliferation, differentiation and cell survival, are regulated by controlling their biosynthesis, catabolism and transport. Antizymes and antizyme inhibitors are key regulatory proteins of polyamine levels by affecting ornithine decarboxylase, the rate-limiting biosynthetic enzyme, and polyamine uptake. We recently described the molecular function of a novel antizyme inhibitor (AZIN2). However, the physiological function of AZIN2 in mammals is mostly unknown. To gain insight on the tissue expression profile of AZIN2 and to find its possible physiological role, we have generated, transgenic mice with severe Azin2 hypomorphism. This mouse model expresses transgenic bacterial β-D-galactosidase as a reporter gene, under the control of the Azin2 endogenous promoter, what allows a very sensitive and specific detection of the expression of the gene in the different tissues of transgenic mice. The biochemical and histochemical analyses of β-D-galactosidase together with the quantification of Azin2 mRNA levels, corroborated that AZIN2 is mainly expressed in testis and brain, and showed for the first time that AZIN2 is also expressed in the adrenal glands and pancreas. In these tissues, AZIN2 was not expressed in all type of cells, but rather in specific type of cells. Thus, AZIN2 was mainly found in the haploid germinal cells of the testis and in different brain regions such as hippocampus and cerebellum, particularly in specific type of neurons. In the adrenal glands and pancreas, the expression was restricted to the adrenal medulla and to the Langerhans islets, respectively. Interestingly, plasma insulin levels were significantly reduced in the transgenic mice. These results support the idea that AZIN2 may have a role in the modulation of reproductory and secretory functions and that this mouse model might be an interesting tool for the progress of our understanding on the role of AZIN2 and polyamines in specific mammalian cells.

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“…by activation of polyamine catabolism in rats overexpressing spermidine/spermine- N 1 -acetyltransferase) described important changes in the ultrastructure of acinar cells, including the presence of early partially degranulated zymogen granules. Furthermore, Kanerva et al [60] have recently described a critical role for AZIN2 in regulating the transport of secretory vesicles by locally activating ODC and polyamine biosynthesis. In this paper, the authors demonstrated selective fragmentation of the TGN and retarded exocytotic release of vesicular stomatitis virus glycoprotein upon RNAi-mediated knockdown of AZIN2 or DFMO-induced cellular polyamine depletion.…”

Section: Discussionmentioning

confidence: 99%

Polyamines Are Present in Mast Cell Secretory Granules and Are Important for Granule Homeostasis

et al. 2010

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BackgroundMast cell secretory granules accommodate a large number of components, many of which interact with highly sulfated serglycin proteoglycan (PG) present within the granules. Polyamines (putrescine, spermidine and spermine) are absolutely required for the survival of the vast majority of living cells. Given the reported ability of polyamines to interact with PGs, we investigated the possibility that polyamines may be components of mast cell secretory granules.Methodology/Principal FindingsSpermidine was released by mouse bone marrow derived mast cells (BMMCs) after degranulation induced by IgE/anti-IgE or calcium ionophore A23187. Additionally, both spermidine and spermine were detected in isolated mouse mast cell granules. Further, depletion of polyamines by culturing BMMCs with α-difluoromethylornithine (DFMO) caused aberrant secretory granule ultrastructure, impaired histamine storage, reduced serotonin levels and increased β-hexosaminidase content. A proteomic approach revealed that DFMO-induced polyamine depletion caused an alteration in the levels of a number of proteins, many of which are connected either with the regulated exocytosis or with the endocytic system.Conclusions/SignificanceTaken together, our results show evidence that polyamines are present in mast cell secretory granules and, furthermore, indicate an essential role of these polycations during the biogenesis and homeostasis of these organelles.

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Ornithine decarboxylase antizyme inhibitor 2 regulates intracellular vesicle trafficking

Cited by 28 publications

References 51 publications

Structural and degradative aspects of ornithine decarboxylase antizyme inhibitor 2

Structural and degradative aspects of ornithine decarboxylase antizyme inhibitor 2

Antizyme Inhibitor 2 Hypomorphic Mice. New Patterns of Expression in Pancreas and Adrenal Glands Suggest a Role in Secretory Processes

Polyamines Are Present in Mast Cell Secretory Granules and Are Important for Granule Homeostasis

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