A RIAM/lamellipodin–talin–integrin complex forms the tip of sticky fingers that guide cell migration

Lagarrigue, Frédéric; Anekal, Praju Vikas; Lee, Ho Sup; Bachir, Alexia I.; Ablack, Jailal; Horwitz, Alan F.; Ginsberg, Mark H.

doi:10.1038/ncomms9492

Cited by 95 publications

(121 citation statements)

References 52 publications

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“…A similar result was also observed when a 5 b 1 integrin was used instead of integrin a IIb b 3 or the formation of Lpdtalin-integrin complexes (50). In this experimental approach, talin-bound Lpd, which is a RIAM paralog present in all species except C. elegans and Drosophila, also formed a complex with a 5 b 1 integrin at the tips of actin-based protrusions.…”

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

confidence: 78%

“…In contrast to RIAM, vinculin is enriched in maturing focal adhesions, which are present on and at the border of lamellipodia, where vinculin reinforces the ability of the adhesion to transmit and bear force (47,49). Live cell imaging combined with indirect bimolecular fluorescence complementation indicated that a RIAM-integrin a IIb b 3 -talin complex is enriched at the tips of growing actin filaments in lamellipodial and filopodial processes, thus revealing the molecular basis of the formation of the so-called sticky fingers of these protrusions (50). Although RIAM is most abundant at the cell edge and lamellipodium, it is subsequently reduced in mature adhesions due to direct competition with vinculin for binding to talin (48).…”

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

confidence: 78%

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

confidence: 99%

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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“…RIAM is essential for inside-out activation of integrins in leukocytes (Klapproth et al, 2015), but surprisingly not in in platelets (Stritt et al, 2015). This suggests that there are alternative pathways, for example, acting through the RIAM paralogue lamellipodin (also known as RAPH1) (Lagarrigue et al, 2015).…”

Section: Recruitment Of Talin To Integrin Adhesion Sitesmentioning

confidence: 99%

Talin – the master of integrin adhesions

Klapholz

Brown

2017

Journal of Cell Science

264

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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“…In fibroblasts, both talins localise to FAs, and talin1 is recruited directly to the leading edge, via proteins like the Rap1 effector RIAM (Rap1‐interacting adapter molecule) 29, 30 and FAK (focal adhesion kinase) 31. In contrast, less is known about talin2 recruitment.…”

Section: The Talinsmentioning

confidence: 99%

The tale of two talins – two isoforms to fine‐tune integrin signalling

Gough

Goult

2018

FEBS Letters

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Talins are cytoplasmic adapter proteins essential for integrin‐mediated cell adhesion to the extracellular matrix. Talins control the activation state of integrins, link integrins to cytoskeletal actin, recruit numerous signalling molecules that mediate integrin signalling and coordinate recruitment of microtubules to adhesion sites via interaction with KANK (kidney ankyrin repeat‐containing) proteins. Vertebrates have two talin genes, TLN1 and TLN2. Although talin1 and talin2 share 76% protein sequence identity (88% similarity), they are not functionally redundant, and the differences between the two isoforms are not fully understood. In this Review, we focus on the similarities and differences between the two talins in terms of structure, biochemistry and function, which hint at subtle differences in fine‐tuning adhesion signalling.

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A RIAM/lamellipodin–talin–integrin complex forms the tip of sticky fingers that guide cell migration

Cited by 95 publications

References 52 publications

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

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

Talin – the master of integrin adhesions

The tale of two talins – two isoforms to fine‐tune integrin signalling

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