Structural and Mechanistic Insights into the Recruitment of Talin by RIAM in Integrin Signaling

Chang, Yu-Chung; Zhang, Hao; Franco‐Barraza, Janusz; Brennan, Mark L.; Patel, Tejash; Cukierman, Edna; Wu, Jiangxue

doi:10.1016/j.str.2014.09.020

Cited by 45 publications

(83 citation statements)

References 47 publications

(85 reference statements)

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“…Known activators include the phosphoinositide PIP2 (Martel et al, 2001), as well as the Rap1 effector RIAM and the heterotrimeric G protein Gα13, both of which bind F3 and displace R9 (Yang et al, 2014;Schiemer et al, 2016), and Kank2, which binds R7 to activate talin (Sun et al, 2016). Both RIAM and PIP2 also contribute to talin activation by bringing it to the membrane Goult et al, 2010;Chang et al, 2014).…”

Section: Regulation Of Talin Interactionsmentioning

confidence: 99%

Talin – the master of integrin adhesions

Klapholz

Brown

2017

Journal of Cell Science

245

222

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Talin has emerged as the key cytoplasmic protein that mediates integrin adhesion to the extracellular matrix. In this Review, we draw on experiments performed in mammalian cells in culture and Drosophila to present evidence that talin is the most important component of integrin adhesion complexes. We describe how the properties of this adaptor protein enable it to orchestrate integrin adhesions. Talin forms the core of integrin adhesion complexes by linking integrins directly to actin, increasing the affinity of integrin for ligands (integrin activation) and recruiting numerous proteins. It regulates the strength of integrin adhesion, senses matrix rigidity, increases focal adhesion size in response to force and serves as a platform for the building of the adhesion structure. Finally, the mechano-sensitive structure of talin provides a paradigm for how proteins transduce mechanical signals to chemical signals.

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Section: Regulation Of Talin Interactionsmentioning

confidence: 99%

Talin – the master of integrin adhesions

Klapholz

Brown

2017

Journal of Cell Science

245

222

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“…This interaction was identified by coimmunoprecipitation using lysates of Chinese hamster ovary (CHO) cells stably expressing integrin a IIb b 3 and transiently cotransfected with hemagglutinin (HA)-tagged talin and various GFP-tagged human RIAM constructs of different lengths (26). Subsequently, it was discovered that the N-terminal domain of RIAM has two distinct TB sites (TBS1 and TBS2), but only TBS1 can recruit talin to the plasma membrane (27). RIAM TBS1 and TBS2 can recognize multiple sites in talin-R (rod) and talin-H (head) F2F3 regions, suggesting that multiple RIAM molecules bind to a single talin molecule.…”

Section: Interaction With Talinmentioning

confidence: 99%

“…However, TBS1, but not TBS2, interacts with talin in the cytoplasm, and the R8 domain of talin, which forms hydrophobic and electrostatic interactions with RIAM, is the strongest binding site for the TBS1 region of RIAM. The interaction of RIAM TBS1 with talin R8 is responsible for recruiting talin to the plasma membrane (27). Furthermore, RIAM TBS1 binds to talin-H region at the F3 subdomain, located in close proximity to the integrin-binding site, which is also located in the F3 subdomain of talin (28).…”

Section: Riam Is An Integral Part Of the Integrin Activation Machinerymentioning

confidence: 99%

“…Moreover, granule polarization and cytotoxicity require Pyk2 activation (95). Given that Pyk2 activation is abrogated in neutrophils from RIAM-null mice (83) and that recruitment of talin to the integrin cytoplasmic tail requires RIAM (27,50), RIAM could play a role in the activation of NK cell cytotoxic functions.…”

Section: The Role Of Riam In Hematopoietic Cells In Vivomentioning

confidence: 99%

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The adaptor molecule RIAM integrates signaling events critical for integrin-mediated control of immune function and cancer progression

et al. 2017

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Lymphocyte activation requires adhesion to antigen-presenting cells. This is a critical event linking innate and adaptive immunity. Lymphocyte adhesion is accomplished through LFA-1, which must be activated by a process referred to as inside-out integrin signaling. Among the few signaling molecules that have been implicated in inside-out integrin activation in hematopoietic cells are the small guanosine triphosphatase (GTPase) Rap1 and its downstream effector Rap1-interacting molecule (RIAM), a multidomain protein that defined the Mig10-RIAM-lamellipodin (MRL) class of adaptor molecules. Through its various domains, RIAM is a critical node of signal integration for activation of T cells, recruits monomeric and polymerized actin to drive actin remodeling and cytoskeletal reorganization, and promotes inside-out integrin signaling in T cells. As a regulator of inside-out integrin activation, RIAM affects multiple functions of innate and adaptive immunity. The effects of RIAM on cytoskeletal reorganization and integrin activation have implications in cell migration and trafficking of cancer cells. We provide an overview of the structure and interactions of RIAM, and we discuss the implications of RIAM functions in innate and adaptive immunity and cancer.

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“…It has been suggested that the small G protein Rap1 (which has two isoforms, Rap1a and Rap1b) is involved in this unmasking process (Han et al, 2006). Upon activation by protein kinase C, Rap1 is localized to the plasma membrane and recruits its effector molecule, Rap1-GTP-interacting adaptor molecule (RIAM, also known as APBB1IP) (Han et al, 2006;Wynne et al, 2012), which binds to talin to reveal the integrin-binding site (Chang et al, 2014;Yang et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Vimentin filaments regulate integrin–ligand interactions by binding to the cytoplasmic tail of integrin β3

Kim

Yang

Kim

et al. 2016

Journal of Cell Science

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Vimentin, an intermediate filament protein induced during epithelialto-mesenchymal transition, is known to regulate cell migration and invasion. However, it is still unclear how vimentin controls such behaviors. In this study, we aimed to find a new integrin regulator by investigating the H-Ras-mediated integrin suppression mechanism. Through a proteomic screen using the integrin β3 cytoplasmic tail protein, we found that vimentin might work as an effector of H-Ras signaling. H-Ras converted filamentous vimentin into aggregates near the nucleus, where no integrin binding can occur. In addition, an increase in the amount of vimentin filaments accessible to the integrin β3 tail enhanced talin-induced integrin binding to its ligands by inducing integrin clustering. In contrast, the vimentin head domain, which was found to bind directly to the integrin β3 tail and compete with endogenous vimentin filaments for integrin binding, induced nuclear accumulation of vimentin filaments and reduced the amount of integrin-ligand binding. Finally, we found that expression of the vimentin head domain can reduce cell migration and metastasis. From these data, we suggest that filamentous vimentin underneath the plasma membrane is involved in increasing integrin adhesiveness, and thus regulation of the vimentin-integrin interaction might control cell adhesion.

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Structural and Mechanistic Insights into the Recruitment of Talin by RIAM in Integrin Signaling

Cited by 45 publications

References 47 publications

Talin – the master of integrin adhesions

Talin – the master of integrin adhesions

The adaptor molecule RIAM integrates signaling events critical for integrin-mediated control of immune function and cancer progression

Vimentin filaments regulate integrin–ligand interactions by binding to the cytoplasmic tail of integrin β3

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