Inositol Pentakis- and Hexakisphosphate Metabolism Adds Versatility to the Actions of Inositol Polyphosphates Novel Effects on Ion Channels and Protein Traffic

Shears, Stephen B.

doi:10.1007/978-1-4613-0343-5_7

Cited by 42 publications

(30 citation statements)

References 171 publications

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“…A new area of signal transduction has recently emerged from the discovery that Ins(3,4,5,6)PÚ down-regulates CaMKII-activated Cl¦ fluxes across the epithelial plasma membrane (see Shears, 1997, andBarrett, 1997, for reviews). It has previously been argued that the action of Ins(3,4,5,6)PÚ upon ClCa was direct, and did not involve any additional cell-signalling components (Ismailov et al 1996).…”

Section: Discussionmentioning

confidence: 99%

“…This is particularly significant from a cell-signalling perspective, because the cellular levels of Ins (3,4,5,6)PÚ are controlled by occupation of appropriate cell-surface receptors. For example, the concentration of Ins (3,4,5,6)PÚ in TÞÚ cells increases from 1 ìÒ to as much as 10-15 ìÒ following PLC activation (Vajanaphanich et al 1995), due to modification of the poise of the Ins(1,3,4,5,6)PÛ 1-phosphatase-Ins(3,4,5,6)PÚ 1_kinase substrate cycle (Shears, 1997;Tan et al 1997). …”

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Regulation of Ca²⁺‐dependent Cl⁻ conductance in a human colonic epithelial cell line (T₈₄): cross‐talk between Ins(3,4,5,6)P₄ and protein phosphatases

Xie

Solomons

Freeman

et al. 1998

The Journal of Physiology

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We have studied the regulation of whole‐cell chloride current in T84 colonic epithelial cells by inositol 3,4,5,6‐tetrakisphosphate (Ins(3,4,5,6)P4). New information was obtained using (a) microcystin and okadaic acid to inhibit serine/threonine protein phosphatases, and (b) a novel functional tetrakisphosphate analogue, 1,2‐bisdeoxy‐1,2‐bisfluoro‐Ins(3,4,5,6)P4 (i.e. F2‐Ins(3,4,5,6)P4). Calmodulin‐dependent protein kinase II (CaMKII) increased chloride current 20‐fold. This current (ICl,CaMK) continued for 7 ± 1.2 min before its deactivation, or running down, by approximately 60 %. This run‐down was prevented by okadaic acid, whereupon ICl,CaMK remained near its maximum value for ≥ 14.3 ± 0.6 min. F2‐Ins(3,4,5,6)P4 inhibited ICl,CaMK (IC50= 100 μM) stereo‐specifically, since its enantiomer, F2‐Ins(1,4,5,6)P4 had no effect at <= 500 μM. Dose‐response data (Hill coefficient = 1.3) showed that F2‐Ins(3,4,5,6)P4 imitated only the non‐co‐operative phase of inhibition by Ins(3,4,5,6)P4, and not the co‐operative phase. Ins(3,4,5,6)P4 was prevented from blocking ICl,CaMK by okadaic acid (IC50= 1.5 nM) and microcystin (IC50= 0.15 nM); these data lead to the novel conclusion that, in situ, protein phosphatase activity is essential for Ins(3,4,5,6)P4 to function. The IC50 values indicate that more than one species of phosphatase was required. One of these may be PP1, since F2‐Ins(3,4,5,6)P4‐dependent current blocking was inhibited by okadaic acid and microcystin with IC50 values of 70 nM and 0.15 nM, respectively.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Regulation of Ca²⁺‐dependent Cl⁻ conductance in a human colonic epithelial cell line (T₈₄): cross‐talk between Ins(3,4,5,6)P₄ and protein phosphatases

Xie

Solomons

Freeman

et al. 1998

The Journal of Physiology

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“…Functional roles for other inositol polyphosphates are emerging (for reviews, see Mennitti et al, 1993;Shears, 1996;Caffrey et al, 1999;Irvine and Schell, 2001). One of these isomers is Ins(3,4,5,6)P 4 , which has been shown to negatively regulate a Ca 2ϩ -activated Cl Ϫ channel that is important for secretion and osmoregulation in epithelial secretory cells (Vajanaphanich et al, 1994;Ismailov et al, 1996;Xie et al, 1996Xie et al, , 1998Barrett et al, 1998;Nilius et al, 1998;Yang et al, 1999;Carew et al, 2000;Ho et al, 2000Ho et al, , 2001.…”

Section: Targets Of Signal Transduction Cascades Mediate Cyclic Behavmentioning

confidence: 99%

Oscillatory Chloride Efflux at the Pollen Tube Apex Has a Role in Growth and Cell Volume Regulation and Is Targeted by Inositol 3,4,5,6-Tetrakisphosphate

et al. 2002

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“…One important consequence of inositol polyphosphates binding to either AP-2 or AP-3 is inhibition of their ability to promote clathrin assembly (5,8,9). Some attention has been drawn to the particularly potent inhibition brought about by InsP 6 , which is also one of the more abundant of the inositol polyphosphates (16). However, it has also been established that inositol lipids can bind to AP-2 and inhibit AP-2-mediated clathrin assembly (5,17).…”

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Regulation of AP-3 Function by Inositides

Hao

Tan

Prasad

et al. 1997

Journal of Biological Chemistry

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As part of the growing effort to understand the role inositol phosphates and inositol lipids play in the regulation of vesicle traffic within nerve terminals, we determined whether or not the synapse-specific clathrin assembly protein AP-3 can interact with inositol lipids. We found that soluble dioctanoyl-phosphatidylinositol 3,4,5-trisphosphate (DiC 8 PtdIns(3,4,5)P 3 ) was only 7.5-fold weaker a ligand than D-myo-inositol hexakisphosphate in assays that measured the displacement of D-myo-[3 H]inositol hexakisphosphate. In functional assays we found that both of these ligands inhibited clathrin assembly, but DiC 8 -PtdIns(3,4,5)P 3 was more potent and exhibited a larger maximal effect. We also examined the structural features of DiC 8 -PtdIns(3,4,5)P 3 that establish specificity. Dioctanoyl-phosphatidylinositol 3,4-bisphosphate, which does not have a 5-phosphate, and 4,5-O-bisphosphoryl-D-myo-inosityl 1-O-(1,2-O-diundecyl)-sn-3-glycerylphosphate, which does not have a 3-phosphate, were, respectively, 2-fold and 4-fold less potent than DiC 8 -PtdIns(3,4,5)P 3 as inhibitors of clathrin assembly. Deacylation of DiC 8 -PtdIns(3,4,5)P 3 reduced its affinity for AP-3 almost 20-fold, and also dramatically lowered its ability to inhibit clathrin assembly. The deacylated products of the soluble derivatives of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate were both not significant inhibitors of clathrin assembly. It therefore appears that the interactions of inositides with AP-3 should not be considered simply in terms of electrostatic effects of the highly charged phosphate groups. Ligand specificity appears also to be mediated by hydrophobic interactions with the fatty-acyl chains of the inositol lipids.There is increasing evidence that certain inositides (members of a large family of inositol phosphates and inositol lipids) act at several levels to regulate both the recruitment and the activation of proteins involved in vesicular transport. PtdIns(3,4,5)P 3 , 1 and the polyphosphoinositide 3-kinase that synthesizes this lipid both feature prominently in this area (1, 2). For example, intracellular trafficking of tyrosine kinase receptors depends upon interactions between the internalized receptors and the 3-kinase (3). Additionally, PtdIns(3,4,5)P 3 interacts either directly or indirectly with several GTPases that play important roles in vesicle traffic (1). Finally, in yeast, the Vps34 protein that is essential for Golgi to vacuole transport is a phosphoinositide 3-kinase (4).Interest in this field is not restricted to the inositol lipids. Other studies into the roles of the inositides in protein traffic have ascertained that certain inositol polyphosphates can bind with high affinity to the clathrin assembly proteins, AP-2 and AP-3 (5-9). AP-2 is believed to play a general role in endocytosis, since it has been found on vesicles budding from the plasma membranes of all types of cells (10). AP-3 is believed to play a more specialized role in synaptic vesicle biogenesis and recycling...

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Inositol Pentakis- and Hexakisphosphate Metabolism Adds Versatility to the Actions of Inositol Polyphosphates Novel Effects on Ion Channels and Protein Traffic

Cited by 42 publications

References 171 publications

Regulation of Ca²⁺‐dependent Cl⁻ conductance in a human colonic epithelial cell line (T₈₄): cross‐talk between Ins(3,4,5,6)P₄ and protein phosphatases

Regulation of Ca²⁺‐dependent Cl⁻ conductance in a human colonic epithelial cell line (T₈₄): cross‐talk between Ins(3,4,5,6)P₄ and protein phosphatases

Oscillatory Chloride Efflux at the Pollen Tube Apex Has a Role in Growth and Cell Volume Regulation and Is Targeted by Inositol 3,4,5,6-Tetrakisphosphate

Regulation of AP-3 Function by Inositides

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Inositol Pentakis- and Hexakisphosphate Metabolism Adds Versatility to the Actions of Inositol Polyphosphates Novel Effects on Ion Channels and Protein Traffic

Cited by 42 publications

References 171 publications

Regulation of Ca2+‐dependent Cl− conductance in a human colonic epithelial cell line (T84): cross‐talk between Ins(3,4,5,6)P4 and protein phosphatases

Regulation of Ca2+‐dependent Cl− conductance in a human colonic epithelial cell line (T84): cross‐talk between Ins(3,4,5,6)P4 and protein phosphatases

Oscillatory Chloride Efflux at the Pollen Tube Apex Has a Role in Growth and Cell Volume Regulation and Is Targeted by Inositol 3,4,5,6-Tetrakisphosphate

Regulation of AP-3 Function by Inositides

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Regulation of Ca²⁺‐dependent Cl⁻ conductance in a human colonic epithelial cell line (T₈₄): cross‐talk between Ins(3,4,5,6)P₄ and protein phosphatases

Regulation of Ca²⁺‐dependent Cl⁻ conductance in a human colonic epithelial cell line (T₈₄): cross‐talk between Ins(3,4,5,6)P₄ and protein phosphatases