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1.
Figure 3

Figure 3. Mechanisms for membrane compartmentalization of PIP2. From: Spatial Segregation of Phosphatidylinositol 4,5-Bisphosphate (PIP2) Signaling in Immune Cell Functions.

(A) Compartmentalized synthesis of PIP2 in membrane rafts by PI4P5K. (B) Partitioning of protein-bound PIP2 to membrane rafts. The yellow spheres represent phosphatidyl 4-inositol, the black represent PIP2.

Corey M. Johnson, et al. Immunol Endocr Metab Agents Med Chem. ;8(4):349-357.
2.
Figure 1

Figure 1. PIP2-dependent T cell signaling pathways for regulation of the actin cytoskeleton. From: Spatial Segregation of Phosphatidylinositol 4,5-Bisphosphate (PIP2) Signaling in Immune Cell Functions.

Actin polymerization and reorganization of the actin cytoskeleton occurs upon triggering of multichain immune recognition receptors (MIRRs). The transduced signals activate intracellular signaling pathways, which are modulated by local PIP2 and PIP3 levels. Three PIP2-dependent pathways for regulation of the actin cytoskeleton are shown here. ERM proteins are membrane-microfilament linkers which when activated (membrane-bound to PIP2 by FERM domain), function in cell adhesion, migration, and morphology. When ERM proteins are deactivated (cytosolic), they allow morphology changes and formation of a mature immune synapse. Vav is localized to the membrane via its PH domain binding to PIP2 and PIP3, and through association with membrane-associated adaptor molecules such as the LAT-associated signalosome in T cells. Vav is an exchange factor for Rho GTPases (Rac, Cdc42), which regulate actin polymerization through different pathways. One important pathway is by activating WASP, which nucleates actin via the Arp 2/3 complex. The integrin LFA-1 is activated by “inside-out” signaling. Abbreviations are: TCR, T cell receptor; PIP2, phosphatidylinositol 4,5-bisphosphate; PIP3, phosphatidylinositol 3,4,5-trisphosphate; PH, pleckstrin homology; ERM, ezrin-radixin-moesin; FERM, band 4.1, ezrin, radixin, moesin; WASP, Wiskott-Aldrich syndrome protein; LAT, linker of activated T cells.

Corey M. Johnson, et al. Immunol Endocr Metab Agents Med Chem. ;8(4):349-357.
3.
Figure 2

Figure 2. Alteration of plasma membrane PIP2 pools by targeted PIP2-specific phosphatase Inp54p. From: Spatial Segregation of Phosphatidylinositol 4,5-Bisphosphate (PIP2) Signaling in Immune Cell Functions.

(A) The PIP2-specific phosphatase Inp54p was targeted to the plasma membrane using separate minimal membrane-anchoring signals. L10 consists of the first 10 amino acids of Lck, and this sequence targeted Inp54p to membrane rafts. S15 contains the first 15 amino acids of Src, and it restricts proteins to the nonraft fraction. To detected transfected cells, each construct contained GFP. A separate control peptide contained the L10 sequence and GFP without the Inp54p. (B) Immunoblots of total lipids extracted from with either the raft or nonraft pools of transfected cells. The antibody was specific to PIP2. The blot shows that expression of the L10-Inp54p resulted in a reduction in the raft-associated pool of PIP2. Expression of the S15-Inp54p caused a decrease in the nonraft PIP2 levels, and a corresponding increase of the PIP2 in membrane rafts. The properties of the targeted Inp54p molecules and the results from their expression are summarized in (C). (D) Expression of the L10-Inp54p and S15- Inp54p caused distinct changes in cell phenotype, including altering cell morphology in transfected T cells Compared to the control, the S15-Inp54p increased membrane ruffling and formation of cell filopodia (arrowheads). In contrast, the L10-Inp54p resulted in smooth cells that were void of ruffles and filopodia. Each image is a three-dimensional projection image of GFP fluorescence generated from confocal image stacks of transfected Jurkat T cells. White bars represent 5 μm.

Corey M. Johnson, et al. Immunol Endocr Metab Agents Med Chem. ;8(4):349-357.

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