Lipid segregation and IgE receptor signaling: A decade of progress

Holowka, David; Gosse, Julie A.; Hammond, Adam T.; Han, Xuemei; Sengupta, Prabuddha; Smith, Norah L.; Wagenknecht-Wiesner, Alice; Wu, Min; Young, Ryan M.; Baird, Barbara

doi:10.1016/j.bbamcr.2005.06.007

Cited by 135 publications

(134 citation statements)

References 62 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…We infer that these events are facilitated by the movement of clustered syndecan-1 into rafts (12), where Src family kinases are present (34). Rafts also provide an environment shielded from transmembrane tyrosine phosphatases (35). Tyrosine phosphorylation of syndecan-1 triggers the robust recruitment of cortactin, which we found to be an essential mediator of efficient actin-dependent endocytosis (Fig.…”

Section: Discussionmentioning

confidence: 99%

Molecular Mediators for Raft-dependent Endocytosis of Syndecan-1, a Highly Conserved, Multifunctional Receptor

Chen

Williams

2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Endocytosis via rafts remains incompletely characterized. Results: Raft-dependent endocytosis of syndecan-1 occurs in two phases, each requiring a kinase and a corresponding cytoskeletal partner. Each phase depends on MKKK, a novel, conserved motif within syndecan-1. Conclusion: These findings demonstrate the molecular choreography behind endocytosis of a raft-dependent receptor. Significance: Syndecans mediate uptake of biologically and medically important ligands.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular Mediators for Raft-dependent Endocytosis of Syndecan-1, a Highly Conserved, Multifunctional Receptor

Chen

Williams

2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Cross-linking of IgE-Fc RI by antigen triggers intracellular signaling events, leading to multiple cellular responses, including degranulation to release chemical mediators that cause inflammatory and allergic reactions. In the earliest signaling events, antigen-induced clustering of IgE-Fc RI causes stable association with ordered lipid domains, wherein the tyrosine kinase Lyn phosphorylates the Fc RI ␤ and ␥ subunits, resulting in recruitment and activation of tyrosine kinase Syk (2,3). Activated Syk phosphorylates a series of proteins resulting in Ca 2ϩ mobilization and other downstream signaling steps leading to degranulation.…”

mentioning

confidence: 99%

Focal adhesion proteins connect IgE receptors to the cytoskeleton as revealed by micropatterned ligand arrays

Torres

Vasudevan

Holowka

et al. 2008

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

Self Cite

View full text Add to dashboard Cite

Patterned surfaces that present specific ligands in spatially defined arrays are used to examine structural linkages between clustered IgE receptors (IgE-Fc RI) and the cytoskeleton in rat basophilic leukemia (RBL) mast cells. We showed with fluorescence microscopy that cytoskeletal F-actin concentrates in the same regions as cell surface IgE-Fc RI that bind to the micrometer-size patterned ligands. However, the proteins mediating these cytoskeletal connections and their functional relevance were not known. We now show that whereas the adaptor proteins ezrin and moesin do not detectably concentrate with the array of clustered IgE-Fc RI, focal adhesion proteins vinculin, paxillin, and talin, which are known to link F-actin with integrins, accumulate in these regions on the same time scale as F-actin. Moreover, colocalization of these focal adhesion proteins with clustered IgE-Fc RI is enhanced after addition of fibronectin-RGD peptides. Significantly, the most prominent rat basophilic leukemia cell integrin (␣5) avoids the patterned regions occupied by the ligands and associates preferentially with exposed regions of the silicon substrate. Thus, spatial separation provided by the patterned surface reveals that particular focal adhesion proteins, which connect to the actin cytoskeleton, associate with ligand-cross-linked IgE-Fc RI, independently of integrins. We investigated the functional role of one of these proteins, paxillin, in IgE-Fc RI-mediated signaling by using small interfering RNA. From these results, we determine that paxillin reduces stimulated phosphorylation of the Fc RI ␤ subunit but enhances stimulated Ca 2؉ release from intracellular stores. The results suggest that paxillin associated with clustered IgE-Fc RI has a net positive effect on Fc RI signaling.FceRI ͉ Lyn ͉ nanobiotechnology ͉ paxillin ͉ supported lipid bilayers C ells have evolved to respond to their chemical and physical environment. Chemical stimulants in the form of soluble or surface-bound ligands are recognized by specific cell surface receptors, and physical cues are sensed by integrins that bind to extracellular matrix proteins on surrounding substrates (1). Cross-talk between intracellular signaling pathways that are initiated by integrins and by ligand receptors has been clearly demonstrated, although spatial aspects of these processes have not been defined. Surfaces patterned on the micrometer scale offer the opportunity to separate regions that bind integrins from those that present ligands to cell surface receptors and thereby delineate respective cytoskeletal connections.The subject of our study is the IgE receptor (Fc RI), which is a member of the family of multisubunit immune recognition receptors that includes antigen receptors on B cells and T cells. This family of receptors has conserved structural features and similarly initiates intracellular signaling in response to multivalent ligands (antigens) that activate cells by clustering cell surface receptors. Fc RI receptors are found primarily in mast cells and basophi...

show abstract

“…The importance of lipid composition for the function of membrane proteins has been demonstrated for a number of relevant proteins involved in signal transduction (6,7) and membrane trafficking (8). Cholesterol is an essential structural component of lipid rafts and caveolae (9,10).…”

mentioning

confidence: 99%

A high-cholesterol diet increases the association between caveolae and insulin receptors in rat liver

Hahn-Obercyger

Graeve

Madar

2009

Journal of Lipid Research

View full text Add to dashboard Cite

Caveolin-1, a component of caveolae, regulates signaling pathway compartmentalization by interacting with tyrosine (Tyr) kinase receptors and their substrates. Perturbations in caveolae lipid composition have been shown in vitro to displace proteins from lipid microdomains, thereby altering their functionality and subsequent downstream signaling. The role of caveolin-1 in insulin receptor (IR) signaling has been widely investigated in vitro mainly in 3T3-L1 adipocyte cells. However, in vivo experiments investigating this connection in liver tissue have not been carried out. The objective of the present study was to investigate the effects of a high-cholesterol diet on caveolin-1 expression and IR localization and activity in the rat liver. Compared with a standard diet, rats fed with diet rich in cholesterol significantly altered liver caveolae by increasing both caveolin-1 (66%, P , 0.05) and caveolin-2 (55%, P , 0.05) expression while caveolin-1 mRNA levels were reduced. Concomitantly, a 25% increase in localization of the caveolae-resident signaling protein IR was observed. The distribution of caveolar and noncaveolar phosphorylated IR was unaffected but insulin-induced IR activation was significantly enhanced following consumption of the high-cholesterol diet (120%, P , 0.001). However, the downstream molecules IRS-1 and Akt have shown impaired activity in cholesterol-fed rats suggesting insulin resistance condition. Insulin stimulation failed to induce Tyr phosphorylation of caveolin-1 in cholesterol-fed rats. These findings suggest a mechanism by which a high-cholesterol diet altered caveolin-1 expression in vivo accompanied by altered IR localization and activity.-Hahn-Obercyger, M., L. Graeve, and Z. Madar. A high-cholesterol diet increases the association between caveolae and insulin receptors in rat liver. J. Lipid Res. 2009. 50: 98-107.

show abstract

Lipid segregation and IgE receptor signaling: A decade of progress

Cited by 135 publications

References 62 publications

Molecular Mediators for Raft-dependent Endocytosis of Syndecan-1, a Highly Conserved, Multifunctional Receptor

Molecular Mediators for Raft-dependent Endocytosis of Syndecan-1, a Highly Conserved, Multifunctional Receptor

Focal adhesion proteins connect IgE receptors to the cytoskeleton as revealed by micropatterned ligand arrays

A high-cholesterol diet increases the association between caveolae and insulin receptors in rat liver

Contact Info

Product

Resources

About