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Understanding the molecular mechanisms of retroviral assembly has been a decades-long endeavor. With the recent discovery of inositol hexakisphosphate (IP6) acting as an assembly co-factor for human immunodeficiency virus (HIV), great strides have been made in retroviral research. In this review, the enzymatic pathways to synthesize and metabolize inositol phosphates (IPs) relevant to retroviral assembly are discussed. The functions of these enzymes and IPs are outlined in the context of the cellular biology important for retroviruses. Lastly, the recent advances in understanding the role of IPs in retroviral biology are surveyed.

Inositol pyrophosphates are unique cellular signaling molecules with recently discovered roles in energy sensing and metabolism. Studies in eukaryotes have revealed that these compounds have a rapid turnover, and thus only small amounts accumulate. Inositol pyrophosphates have not been the subject of investigation in plants even though seeds produce large amounts of their precursor, myo-inositol hexakisphosphate (InsP6 ). Here, we report that Arabidopsis and maize InsP6 transporter mutants have elevated levels of inositol pyrophosphates in their seed, providing unequivocal identification of their presence in plant tissues. We also show that plant seeds store a little over 1% of their inositol phosphate pool as InsP7 and InsP8 . Many tissues, including, seed, seedlings, roots and leaves accumulate InsP7 and InsP8 , thus synthesis is not confined to tissues with high InsP6 . We have identified two highly similar Arabidopsis genes, AtVip1 and AtVip2, which are orthologous to the yeast and mammalian VIP kinases. Both AtVip1 and AtVip2 encode proteins capable of restoring InsP7 synthesis in yeast mutants, thus AtVip1 and AtVip2 can function as bonafide InsP6 kinases. AtVip1 and AtVip2 are differentially expressed in plant tissues, suggesting non-redundant or non-overlapping functions in plants. These results contribute to our knowledge of inositol phosphate metabolism and will lay a foundation for understanding the role of InsP7 and InsP8 in plants., (© 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.)

InsP6 is abundant in cereals and legumes. InsP6 and lower inositol phosphates, in particular InsP3, participate in important intracellular processes. In addition, InsP6 possess significant health benefits, such as anti-cancer effect, kidney stones prevention, lowering serum cholesterol. Because of the insensitivity of existing methods for determination of non-radiolabeled inositol phosphates, little is known about the natural occurrence, much less on the concentrations of InsP6 and InsP3 in biological samples. Using gas chromatography-mass detection analysis of HPLC chromatographic fractions, we report a measurement of unlabeled total InsP3 and InsP6 (a) as they occur within cells culture, tissues, and plasma, and (b) their changes depending on the presence of exogenous InsP6. When rats were fed on a purified diet in which InsP6 was undetectable (AIN-76A) the levels of InsP6 in brain were 3.35 ± 0.57 (SE) μmol·kg−1 and in plasma 0.023 ± 0.008 (SE) μmol·l−1. The presence of InsP6 in diet dramatically influenced its levels in brain and in plasma. When rats were given an InsP6-sufficient diet (AIN-76A + 1% InsP6), the levels of InsP6 were about 100-fold higher in brain tissues (36.8 ± 1.8 (SE)) than in plasma (0.29 ± 0.02 (SE)); InsP6 concentrations were 8.5-fold higher than total InsP3 concentrations in either plasma (0.033 ± 0.012 (SE)) and brain (4.21 ± 0.55 (SE)). When animals were given an InsP6-poor diet (AIN-76A only), there was a 90% decrease in InsP6 content in both brain tissue and plasma (p < 0.001); however, there was no change in the level of total InsP3. In non-stimulated malignant cells (MDA-MB 231 and K562) the InsP6 contents were 16.2 ± 9.1 (SE) μmol·kg−1 for MDA-MB 231 cells and 15.6 ± 2.7 (SE) for K 562 cells. These values were around 3-fold higher than those of InsP3 (4.8 ± 0.5 μmol·kg−1 and 6.9 ± 0.1 (SE) for MDA-MB 231 and K562 cells respectively). Treatment of malignant cells with InsP6 resulted in a 2-fold increase in the intracellular concentrations of total InsP3 (9.5 ± 1.3 (SE) and 10.8 ± 1.0 (SE) μmol·kg−1 for MDA-MB 231 and K562 cells respectively, p < 0.05), without changes in InsP6 levels. These results indicate that exogenous InsP6 directly affects its physiological levels in plasma and brain of normal rats without changes on the total InsP3 levels. Although a similar fluctuation of InsP6 concentration was not seen in human malignant cell lines following InsP6 treatment, an increased intracellular levels of total InsP3 was clearly observed. [Copyright &y& Elsevier]

Visual arrestin (Arr1) terminates rhodopsin signaling by blocking its interaction with transducin. To do this, Arr1 translocates from the inner to the outer segment of photoreceptors upon light stimulation. Mounting evidence indicates that inositol phosphates (InsPs) affect Arr1 activity, but the Arr1-InsP molecular interaction remains poorly defined. We report the structure of bovine Arr1 in a ligand-free state featuring a near-complete model of the previously unresolved C-tail, which plays a crucial role in regulating Arr1 activity. InsPs bind to the N-domain basic patch thus displacing the C-tail, suggesting that they prime Arr1 for interaction with rhodopsin and help direct Arr1 translocation. These structures exhibit intact polar cores, suggesting that C-tail removal by InsP binding is insufficient to activate Arr1. These results show how Arr1 activity can be controlled by endogenous InsPs in molecular detail. [Display omitted] • The regulatory C-tail/N-domain interaction of arrestin-1 is resolved • Arrestin-1 binds InsPs using many of the same residues that hold the C-tail • InsP binding does not activate arrestin-1, but partially removes the C-tail Sander et al. resolve how the C-tail regulatory domain and the N-domain of arrestin 1 interact and maintain correct cellular localization. They further show that InsPs, including InsP 3 , compete for N-domain contacts responsible for binding the C-tail, thereby priming the structure for translocation. [ABSTRACT FROM AUTHOR]