Actin restricts FcɛRI diffusion and facilitates antigen-induced receptor immobilization

Andrews, Nicholas L.; Lidke, Keith A.; Pfeiffer, Janet R.; Burns, Alan R.; Wilson, Bridget S.; Oliver, Janet M.; Lidke, Diane S.

doi:10.1038/ncb1755

Cited by 276 publications

(378 citation statements)

References 44 publications

Supporting

Mentioning

344

Contrasting

Order By: Relevance

“…The existence of preformed dimers stabilized by indirect interactions is supported by the observation of such transient protein clusters in which the distance between proteins is larger than the range of direct molecular interactions. Therefore, these clusters do not constitute stable molecular associations such as those arising after ligand binding (45).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, hetero-FRET cannot discriminate between small and large aggregates, because cluster size only slightly affects the transfer efficiency (43), whereas homo-FRET is more suitable for the detection of higher-order associations (22,38,44). In addition, methods based on the measurement of fluorescence correlations, including N&B analysis, detect joint mobility, which can arise not only from tight molecular associations, but also by mutual confinement by membrane structures (45). The use of image correlation techniques [image correlation spectroscopy or dynamic image correlation spectroscopy (DICS)] (27,46) to determine molecular associations applied to fixed cells is much less reliable due to fixation artifacts, photon statistics, and the optical resolution of the microscope.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Distribution of resting and ligand-bound ErbB1 and ErbB2 receptor tyrosine kinases in living cells using number and brightness analysis

Nagy

Claus

Jovin

et al. 2010

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

156

View full text Add to dashboard Cite

Ligand-driven dimerizations of ErbB receptor subunits fulfill a fundamental role in their activation. We have used the number and brightness analysis technique to investigate the existence of preformed ligand-independent dimers and clusters and to characterize the initial steps in the activation of ErbB1 and ErbB2. In cells expressing 50,000-200,000 receptors, ErbB1 was monomeric in the absence of ligand stimulation, whereas in CHO cells with receptor levels >500,000 as much as 30% of ErbB1 was present as preformed dimers. EGF induced the formation of ErbB1 dimers as well as larger clusters (up to pentamers) that colocalized with clathrin-coated pits. The distribution of unstimulated ErbB2 in cells expressing 3·10 5 − 10 6 receptors was fundamentally different, in that this receptor was present in preformed homoassociated aggregates containing 5-10 molecules. These constitutive ErbB2 homoclusters colocalized with caveolae, increased in size at subphysiological temperatures, but decreased in size upon EGF stimulation. We conclude that these ErbB2 clusters are promoted primarily by membrane-mediated interactions and are dispersed upon ligand stimulation.EGFR | epidermal growth factor | ErbB proteins | receptor clusters | signal transduction E rbB proteins (ErbB1-4, HER1-4) constitute the best characterized family of receptor tyrosine kinases (1). Biochemical analysis has demonstrated that ErbB1, the prototypical member of the family (also known as the epidermal growth factor receptor, EGFR or HER1) undergoes ligand-induced homodimerization as a key step in its activation (2). More recent crystallographic studies reveal that ligand binding induces a transition from a closed conformation of ErbB1 to an extended configuration with the capacity to dimerize via intermolecular interactions mediated by domain II (3, 4). The ultrastructural data also confirm that dimerization of ErbB1 plays a fundamental role in activating the kinase domain by a mechanism resembling that of cyclin dependent kinases (5, 6). The coreceptor ErbB2 has no known ligand but upon transactivation expresses the most potent kinase activity of the ErbB family, thereby increasing the efficiency of signaling mediated by ErbB2-containing heterodimers (7). ErbB2 constitutively adopts an extended conformation potentiating the formation of heterodimers (8, 9) that can be inhibited by pertuzumab, a monoclonal antibody sterically blocking the heterodimerization arm of ErbB2 (10). Although the extracellular domain of ErbB2 has failed to form crystallographic homodimers, molecular biological and fluorescence resonance energy transfer (FRET) experiments have shown that full-length ErbB2 exists in dimers or higher-order aggregates in the plasma membrane (11,12). The implication is that the transmembrane, juxtamembrane and other intracellular domains (5, 13, 14) act in conjunction with the membrane environment (15) to mediate the dimerization and, thereby, functional states of ErbB proteins.Many investigators have sought to determine the distribution of ErbB1 in ...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Distribution of resting and ligand-bound ErbB1 and ErbB2 receptor tyrosine kinases in living cells using number and brightness analysis

Nagy

Claus

Jovin

et al. 2010

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

156

View full text Add to dashboard Cite

show abstract

“…Ample experimental evidence indicates that EGF receptors can have a highly inhomogeneous distribution characterized by small areas of high density [30], and exhibit anomalous diffusion [20]. There are other examples of receptors that exhibit clustering and anomalous diffusion [1]. Receptor accumulation in high density patches has an impact on dimerization and on signaling [3,9,[15][16][17].…”

Section: The Microscopic Picturementioning

confidence: 99%

“…Each of the six species is presented in both domains; similary, each of the 7 reactions has a copy in each domain, see Figure 4. Assuming the free VEGF concentration is kept constant at V 0 , we have a 12-dimensional state vector, (1) In addition to the 28 (irreversible) reactions that represent molecular transformations, we describe the transfer of every molecular species between domains as a separate reaction, bringing the total to 40 (irreversible) reactions. It is convenient to group pairs of opposing reactions into single reversible reactions [11], leaving us with 20 reversible reactions, as illustrated in Figure 4.…”

Section: Reactions and Equationsmentioning

confidence: 99%

“…The current picture [28] is more structured, with microdomains of lipids and proteins [6,13,24]. Modern microscopy techniques [22,29] provide direct evidence of the effect of these structures on membrane receptor localization and movement [1,18,20], revealing receptor clusters in static images, and intervals of confinement in small areas separated by jumps or "hops" in single particle tracking.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The impact of high density receptor clusters on VEGF signaling

Chen

Short

Halász

et al. 2013

Electron. Proc. Theor. Comput. Sci.

View full text Add to dashboard Cite

Vascular endothelial growth factor (VEGF) signaling is involved in the process of blood vessel development and maintenance. Signaling is initiated by binding of the bivalent VEGF ligand to the membrane-bound receptors (VEGFR), which in turn stimulates receptor dimerization. Herein, we discuss experimental evidence that VEGF receptors localize in caveloae and other regions of the plasma membrane, and for other receptors, it has been shown that receptor clustering has an impact on dimerization and thus also on signaling. Overall, receptor clustering is part of a complex ecosystem of interactions and how receptor clustering impacts dimerization is not well understood. To address these questions, we have formulated the simplest possible model. We have postulated the existence of a single high affinity region in the cell membrane, which acts as a transient trap for receptors. We have defined an ODE model by introducing high-and low-density receptor variables and introduce the corresponding reactions from a realistic model of VEGF signal initiation. Finally, we use the model to investigate the relation between the degree of VEGFR concentration, ligand availability, and signaling. In conclusion, our simulation results provide a deeper understanding of the role of receptor clustering in cell signaling.

show abstract

Membrane Dynamics: Fluorescence Spectroscopy

Subburaj

Gallego

García‐Sáez

2000

Encyclopedia of Analytical Chemistry

View full text Add to dashboard Cite

Membranes are dynamic lipophilic structures that constitute a selective barrier essential for the smooth functioning of cellular machinery. Their complex and highly heterogeneous composition, as well as the intricate diffusion patterns that they display, have been intensely studied in the past decades. Several innovative microscopy techniques have recently been developed to gain insight into the basis of membrane dynamics, interactions, and molecular organization. In this article, we introduce four pioneer fluorescence‐based approaches that have substantially broadened our overall understanding of membranes: fluorescence correlation spectroscopy (FCS), single particle tracking (SPT), fluorescence recovery after photobleaching (FRAP), and 6‐lauroyl‐2‐(dimethylamino)‐naphtalene (LAURDAN) microscopy. We discuss each technique in detail, explaining their principles, methodology, and applications in the research of the dynamic processes controlled by membranes.

show abstract

Actin restricts FcɛRI diffusion and facilitates antigen-induced receptor immobilization

Cited by 276 publications

References 44 publications

Distribution of resting and ligand-bound ErbB1 and ErbB2 receptor tyrosine kinases in living cells using number and brightness analysis

Distribution of resting and ligand-bound ErbB1 and ErbB2 receptor tyrosine kinases in living cells using number and brightness analysis

The impact of high density receptor clusters on VEGF signaling

Membrane Dynamics: Fluorescence Spectroscopy

Contact Info

Product

Resources

About