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1.
Figure 2

Figure 2. From: Regulation from within: the cytoskeleton in transmembrane signaling.

Interaction of immunoreceptors with multivalent targets. a) Individually confined/anchored receptors. Left panel: ‘biophysical’ view of receptors with limited diffusion range, indicated by dotted circles (see Figure 1 for details of this and subsequent left panels). Right panel: because the mobility of receptors is limited, clustering by exposure to vicinal ligands (fuchsia circles) on target (blue) is ineffective. b) Receptors undergoing hop-diffusion. Left panel: ‘biophysical’ view of two hop-diffusing receptors. Right panel: hop-diffusing receptors can gradually move along the surface of the membrane, and can therefore undergo target-induced clustering, albeit slowly. c) Co-confined or co-anchored receptors. Left panel: ‘biophysical’ view of multiple receptors restricted to diffuse within individual corrals. Right panel: fast association of several receptors with multivalent target when the latter collides with region of receptor co-confinement. d) Co-confined or co-anchored receptors with tendency to self-associate. Left panel: ‘biophysical’ view of multiple receptors that have the tendency to self-associate transiently and are restricted to diffuse within individual corrals. Right panel: self-associating receptors will bind rapidly and very effectively to multivalent target when the latter collides with region of receptor co-confinement.

Khuloud Jaqaman, et al. Trends Cell Biol. 2012 October;22(10):515-526.
2.
Figure 3

Figure 3. From: Regulation from within: the cytoskeleton in transmembrane signaling.

Signal transduction by immunoreceptors. a) Resting state. The membrane consists of cholesterol-depleted regions (beige) and cholesterol-enriched nanodomains (rafts; brown). Cholesterol is shown in red. Src-family kinases (SFKs) are anchored to the membrane by acylation and can exist in an unphosphorylated state or be phosphorylated at an inhibitory site (yellow circle labeled P with red perimeter). CD45, a tyrosine phosphatase, can dephosphorylate SFKs, facilitating their activation. Inactivated immunoreceptors (dark blue) reside largely outside rafts. Their tyrosine residues (cyan hexagons labeled Y) constituting the ITAM motif are buried in the bilayer. Co-receptors (red), present mostly in rafts, tend to associate with SFKs. b) Signal initiation. A target (light blue) bearing ligands for the immunoreceptors (green diamonds) and co-receptors (fuchsia circles) cluster immunoreceptors and co-receptors together in the context of rafts, where active SFKs can autophosphorylate (yellow circle labeled P with green perimeter) to stabilize their active state, and can phosphorylate and activate the ITAM tyrosines on immunoreceptors (also yellow circle labeled P with green perimeter). c) Signal propagation. Dually phosphorylated tyrosines at the ITAM motif attract tandem SH2 domains of Syk or ZAP70 (S/Z). Recruited Syk or ZAP70 can in turn be tyrosine phosphorylated and activated by SFKs and by autophosphorylation, thereby propagating the signal.

Khuloud Jaqaman, et al. Trends Cell Biol. 2012 October;22(10):515-526.
3.
Figure 1

Figure 1. From: Regulation from within: the cytoskeleton in transmembrane signaling.

Types of motion of membrane proteins. a) Free diffusion, as experienced by a protein in a lipid bilayer. Left panel: ‘biophysical’ view illustrating the trajectory of a molecule. Each segment of the line indicates the displacement recorded using a fast rate of image acquisition. Right panel: molecular view illustrating the lipids constituting the bilayer (beige; in all panels) and a transmembrane protein (red; in all panels). The arrows indicate the ability of the protein to diffuse in any direction. b) Anchorage/tethering, experienced by a protein while directly or indirectly associated with the cortical cytoskeleton. Left panel: ‘biophysical’ view illustrating that the mobility of a transmembrane protein is restricted to a limited area (dotted circle) as a result of its attachment to cytoskeletal filaments (gray rods; in all panels). Right panel: molecular view illustrating attachment of the transmembrane protein to the cytoskeleton, in this illustration by association of its cytoplasmic tail to an adaptor linker molecule (blue). Shorter arrows imply restricted mobility. c) Hop-diffusion, experienced by a protein temporarily trapped within corrals formed by picket-fences that form on the cytoskeleton. Left panel: ‘biophysical’ view illustrating that the protein diffuses rapidly within the corral (red lines) but only occasionally escapes from one corral to the next, resulting in eventual long-range displacement, observable at slower rates of image acquisition (black line). Middle panel: illustrates the confinement of a transmembrane protein by a picket-fence constituted by various proteins (all non-red cylinders) that are attached directly or indirectly (via a blue adaptor) to the cytoskeleton. Right panel: transient opening of the fence – either because of detachment of pickets from the cytoskeleton or due to remodeling of the skeleton itself – enables the diffusible protein to escape the corral (gray arrow). d) Confined diffusion, experienced by a protein trapped within corrals formed by picket-fences that form on the cytoskeleton. Left panel: ‘biophysical’ view illustrating that the protein diffuses rapidly within the corral (red lines) but cannot escape (at least during the course of the recording). Right panel: confinement of a diffusible protein by a picket-fence constituted by various other proteins that are attached directly or indirectly (via blue adaptors) to the cytoskeleton. Not shown is the case where the cytoplasmic domain of the transmembrane protein itself bumps into the cortical cytoskeleton, leading to its hop-diffusion (c) or long-term confinement (d).

Khuloud Jaqaman, et al. Trends Cell Biol. 2012 October;22(10):515-526.

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