Subcellular Localization of Talin Is Regulated by Inter-domain Interactions

Abstract

Background: Talin regulates integrin affinity and nucleates the integrin-cytoskeleton linkage at the plasma membrane. Results: Specific inter-domain interactions between the talin head and two rod regions block interaction with actin or plasma membrane localization. Conclusion: Autoinhibitory interactions between the talin head and rod domains maintain cytosolic talin. Significance: Structurally defined inter-domain interactions regulate talin localization and function.

Phosphatidylinositol Phosphate 5-Kinase Iγi2 in Association with Src Controls Anchorage-independent Growth of Tumor Cells

“…In the absence of cell-matrix interactions in suspension culture, all of them are assembled into a complex, presumably at the vicinity of integrins and growth factor receptors that sustain oncogenic signaling necessary for anchorage-independent growth. In three-dimensional culture, their mutual interaction may promote their organization at cell-cell contact sites in the plasma membrane, although their major fractions remain in cytosol (22,44,45). Furthermore, Src is required for PIPKI␥i2 association with talin in different tumor cells (not shown), and Src expression significantly promoted PIPKI␥i2 association with talin.…”

A novel membrane-dependent on/off switch mechanism of talin FERM domain at sites of cell adhesion

“…Since the membrane-binding of talin-FERM is essential for its access to integrin β CT membrane-proximal region and for enhancing the talin-FERM/integrin interaction [13][14][15][16][17], the repulsion mechanism by talin-RS may represent an effective way to negatively regulate this targeting process, which in turn promotes the cytosolic retention of the latent talin. A recent report suggested that talin-R 482-787 fragment (talin-R1) may also interact with talin-F2F3 and inhibits the talin-FERM/membrane interaction [32]. However, as compared to the potent talin-RS/ talin-F2F3 interaction, the binding of talin-R1 to talin-F2F3 appears to be very weak or non-specific, since no significant chemical shift changes were observed even when talin-R1 was in excess [19,32] except for some NMR line-broadening that occurred when even more excess talin-R1 was added to 15 N-labeled talin-F2F3 [32].…”

“…A recent report suggested that talin-R 482-787 fragment (talin-R1) may also interact with talin-F2F3 and inhibits the talin-FERM/membrane interaction [32]. However, as compared to the potent talin-RS/ talin-F2F3 interaction, the binding of talin-R1 to talin-F2F3 appears to be very weak or non-specific, since no significant chemical shift changes were observed even when talin-R1 was in excess [19,32] except for some NMR line-broadening that occurred when even more excess talin-R1 was added to 15 N-labeled talin-F2F3 [32]. Further investigation such as obtaining the structures of full-length talin and talin-binding partners is clearly necessary to examine the existence of additional mechanisms that stabilize retention of the latent talin in the cytosol.…”

Talin – the master of integrin adhesions

“…Two intramolecular interactions between the head and rod have been mapped: between R9 and F3, masking IBS1 (Goksoy et al, 2008;Goult et al, 2009;Zhang et al, 2016), and between R1-R2 and F2-F3, potentially masking membranebinding regions of talin head (Banno et al, 2012). Disrupting the In the cytoplasm, the talin dimer has a closed conformation and has to be opened up to be able to interact with integrins.…”

“…interaction between R9 and F3 enhances actin binding by talin (Banno et al, 2012), promotes integrin activation (Zhang et al, 2016), and increases focal adhesion number and assembly rate . In the developing Drosophila embryo, this disruption increases the size of focal adhesion-like structures, retarding epithelial morphogenesis (Ellis et al, 2013).…”