The PI(3,5)P2 and PI(4,5)P2 Interactomes

Catimel, Bruno; Schieber, Christine; Condron, Melanie; Patsiouras, Heather; Connolly, Lisa; Catimel, Jenny; Nice, Edouard C.; Burgess, Antony W.; Holmes, Andrew B.

doi:10.1021/pr800540h

Cited by 87 publications

(128 citation statements)

References 130 publications

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“…It has been reported that talin FERM domains bind to negatively charged vesicles in solution (12,13,24,31,32). To confirm these observations, we used isothermal titration calorimetry (ITC) to measure the enthalpy of F0-F3 binding to large unilamellar vesicles (LUVs) composed of 90% POPC and 10% PtdInsð4;5ÞP 2 .…”

Section: Resultsmentioning

confidence: 81%

“…Similarly, the cytoskeletal protein talin-1, whose binding to the β3 cytosolic tail (CT) stabilizes the active conformation of αIIbβ3 (6)(7)(8), is sequestered away from the β3 CT (9). Besides interacting with integrins, talin-1 interacts with negatively charged phospholipids (10)(11)(12) and phosphoinositides (13)(14)(15)(16). Stimuli generated at sites of vascular damage recruit talin-1 to the platelet plasma membrane, thereby promoting αIIbβ3 activation (17)(18)(19).…”

mentioning

confidence: 99%

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Affinity of talin-1 for the β3-integrin cytosolic domain is modulated by its phospholipid bilayer environment

Moore

Nygren

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Binding of the talin-1 FERM (4.1/ezrin/radixin/moesin) domain to the β3 cytosolic tail causes activation of the integrin αIIbβ3. The FERM domain also binds to acidic phospholipids. Although much is known about the interaction of talin-1 with integrins and lipids, the relative contribution of each interaction to integrin regulation and possible synergy between them remain to be clarified. Here, we examined the thermodynamic interplay between FERM domain binding to phospholipid bilayers and to its binding sites in the β3 tail. We found that although both the F0F1 and F2F3 subdomains of the talin-1 FERM domain bind acidic bilayers, the full-length FERM domain binds with an affinity similar to F2F3, indicating that F0F1 contributes little to the overall interaction. When free in solution, the β3 tail has weak affinity for the FERM domain. However, appending the tail to acidic phospholipids increased its affinity for the FERM domain by three orders of magnitude. Nonetheless, the affinity of the FERM for the appended tail was similar to its affinity for binding to bilayers alone. Thus, talin-1 binding to the β3 tail is a ternary interaction dominated by a favorable surface interaction with phospholipid bilayers and set by lipid composition. Nonetheless, interactions between the FERM domain, the β3 tail, and lipid bilayers are not optimized for a high-affinity synergistic interaction, even at the membrane surface. Instead, the interactions appear to be tuned in such a way that the equilibrium between inactive and active integrin conformations can be readily regulated.cytoskeleton | plasma membrane | platelet aggregation T he integrin αIIbβ3 resides on the platelet surface in equilibrium between resting and active conformations (1-5). On circulating platelets, αIIbβ3 is constrained in its inactive conformation to prevent spontaneous platelet aggregation. Similarly, the cytoskeletal protein talin-1, whose binding to the β3 cytosolic tail (CT) stabilizes the active conformation of αIIbβ3 (6-8), is sequestered away from the β3 CT (9). Besides interacting with integrins, talin-1 interacts with negatively charged phospholipids (10-12) and phosphoinositides (13)(14)(15)(16). Stimuli generated at sites of vascular damage recruit talin-1 to the platelet plasma membrane, thereby promoting αIIbβ3 activation (17-19). Much is known about the interaction of talin-1 with integrins and lipids, but the relative contribution of each interaction to integrin regulation and possible synergy between them remain to be clarified. Elucidating these interactions is important for understanding events leading to and controlling the formation of integrin complexes and for potential pharmacologic modulation of integrin signaling.Talin-1 is a 250-kD protein containing a 45-kD N-terminal head domain attached via a flexible linker to a 200-kD C-terminal rod domain (7). Because the head domain is packed against the rod domain in its inactive state (20), talin-1 recruitment to the membrane and to integrin β CTs requires disruption of this interaction (1...

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Section: Resultsmentioning

confidence: 81%

mentioning

confidence: 99%

Affinity of talin-1 for the β3-integrin cytosolic domain is modulated by its phospholipid bilayer environment

Moore

Nygren

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…HRMS and 1 H, 13 C, and 31 P NMR spectra of all new compounds reported in this paper are available on the Journal's website.…”

Section: Supplementary Materialsmentioning

confidence: 99%

“…[8] The synthetic derivatives of these molecules were used to form liposomes for characterisation purposes. [13,14] However, it is not always desirable to form liposomes or higher-order aggregates when studying such compounds. Furthermore, the long-acyl-chain derivatives are not particularly soluble in water owing to their hydrophobicity, which can cause problems when studying the interactions of such compounds with polar macromolecules.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Highly Water-Soluble Adamantyl Phosphoinositide Derivatives

et al. 2015

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Phosphatidylinositol phosphates are key regulators of cell signalling pathways and membrane trafficking in eukaryotic cells, and there is a need for new chemical probes to further understand how they interact with lipid-binding proteins. Here, the synthesis of phosphatidylinositol phosphate analogues containing adamantyl carboxylic ester groups, in place of the natural lipid side chains, is described. These derivatives are considerably more soluble in water than analogues containing other lipid side chains and do not form large aggregates such as liposomes or micelles. These adamantyl analogues bind to known phosphoinositide-binding proteins with similar affinities to native ligands and will facilitate future studies on the substrate specificities of these proteins involving cocrystallisation studies with proteins.

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“…None of these proteins overlapped with the ones identified in the previous study. In a more comprehensive study, Holmes and colleagues have characterized and compared the interactomes of PtdIns(3,5)P 2 and PtdIns(4,5)P 2 (Catimel et al 2008) as well as PtdIns(3,4,5)P 3 (Catimel et al 2008;Catimel et al 2009) determined from the cytosolic extracts of colon cancer cells expressing WT PI3 kinase. PIs immobilized either onto beads or incorporated into liposomes were used for protein capture from the cytosolic extracts.…”

Section: Lipid-protein Interactomesmentioning

confidence: 99%