AMPK negatively regulates tensin-dependent integrin activity

Γεωργιάδου, Μαρία; Lilja, Johanna; Jacquemet, Guillaume; Guzmán, Camilo; Rafaeva, Maria; Charlotte, A. Cockram; Yan, Yan; Sahgal, Pranshu; Lerche, Martina; Manneville, Jean‐Baptiste; Mäkelä, Tomi P.; Ivaska, Johanna

doi:10.1083/jcb.201609066

Cited by 97 publications

(115 citation statements)

References 65 publications

Supporting

Mentioning

108

Contrasting

Order By: Relevance

“…The talin head alone can shift the integrin conformation towards an active state (Box 1), but there is increasing evidence that forces generated by actin polymerisation and myosin contraction are involved in inducing or stabilising the extended-open conformation (Comrie et al, 2015;Nordenfelt et al, 2016). This additional mechanism fits well with the discovery of other IAPs that cooperate with talin to activate integrins, such as kindlins, although the mechanism is still unclear and kindlins also cluster integrins (Moser et al, 2009;Calderwood et al, 2013;Ye et al, 2013;Rognoni et al, 2016;Georgiadou et al, 2017). Additional IAPs enhancing talinmediated activation are RIAM (Han et al, 2006;Yang et al, 2014), zasp (also known as LDB3) (Bouaouina et al, 2012) and vinculin (Lee et al, 2013), whereas other IAPs compete with talin and reduce activation, including ICAP1 (also known as ITGB1BP1) (Bouvard et al, 2003), filamin A (Kiema et al, 2006) and moesin (Vitorino et al, 2015).…”

Section: Talin In Integrin Activationsupporting

confidence: 48%

Talin – the master of integrin adhesions

Klapholz

Brown

2017

Journal of Cell Science

264

222

View full text Add to dashboard Cite

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.

show abstract

Section: Talin In Integrin Activationsupporting

confidence: 48%

Talin – the master of integrin adhesions

Klapholz

Brown

2017

Journal of Cell Science

264

222

View full text Add to dashboard Cite

show abstract

“…This is consistent with other studies, and suggests that AMPK regulates the endocytic membrane traffic of integrins during metabolic stress. AMPK negatively regulates the expression of tensin, which binds integrins to promote integrin‐dependent adhesion and other processes . Thus, AMPK likely directs control of cell migration, adhesion and signaling via both acute alterations of endocytic traffic and prolonged adaptation resulting from alterations in gene expression.…”

Section: Control Of Endocytic Membrane Traffic By Ampkmentioning

confidence: 99%

Energetic adaptations: Metabolic control of endocytic membrane traffic

Rahmani

Defferrari

Wakarchuk

et al. 2019

Traffic

View full text Add to dashboard Cite

Endocytic membrane traffic controls the access of myriad cell surface proteins to the extracellular milieu, and thus gates nutrient uptake, ion homeostasis, signaling, adhesion and migration. Coordination of the regulation of endocytic membrane traffic with a cell's metabolic needs represents an important facet of maintenance of homeostasis under variable conditions of nutrient availability and metabolic demand. Many studies have revealed intimate regulation of endocytic membrane traffic by metabolic cues, from the specific control of certain receptors or transporters, to broader adaptation or remodeling of the endocytic membrane network. We examine how metabolic sensors such as AMP‐activated protein kinase, mechanistic target of rapamycin complex 1 and hypoxia inducible factor 1 determine sufficiency of various metabolites, and in turn modulate cellular functions that includes control of endocytic membrane traffic. We also examine how certain metabolites can directly control endocytic traffic proteins, such as the regulation of specific protein glycosylation by limiting levels of uridine diphosphate N‐acetylglucosamine (UDP‐GlcNAc) produced by the hexosamine biosynthetic pathway. From these ideas emerge a growing appreciation that endocytic membrane traffic is orchestrated by many intrinsic signals derived from cell metabolism, allowing alignment of the functions of cell surface proteins with cellular metabolic requirements. Endocytic membrane traffic determines how cells interact with their environment, thus defining many aspects of nutrient uptake and energy consumption. We examine how intrinsic signals that reflect metabolic status of a cell regulate endocytic traffic of specific proteins, and, in some cases, exert broad control of endocytic membrane traffic phenomena. Hence, endocytic traffic is versatile and adaptable and can be modulated to meet the changing metabolic requirements of a cell.

show abstract

“…Loss of AMPK promotes tensin expression, in turn leading to β1 activation and FN fibrillogenesis in fibroblasts (Georgiadou et al . ). It has been hypothesized that, within this FN‐rich environment, cancer cells can take up the ECM deposited by cancer‐associated fibroblasts, for the generation of the nutrients required to support cell proliferation and tumour growth (Georgiadou & Ivaska ).…”

Section: Ecm Traffic and Metabolismmentioning

confidence: 97%

Extracellular matrix internalization links nutrient signalling to invasive migration

Rainero

2018

Int J Experimental Path

View full text Add to dashboard Cite

Integrins are the key mediators of cell-extracellular matrix (ECM) interaction, linking the ECM to the actin cytoskeleton. Besides localizing at the cell surface, they can be internalized and transported back to the plasma membrane (recycled) or delivered to the late endosomes/lysosomes for degradation. We and others have shown that integrin can be endocytosed together with their ECM ligands. In this short review, I will highlight how extracellular protein (including ECM) endocytosis impinges on the activation of the mechanistic target of rapamycin (mTOR) pathway, a master regulator of cell metabolism and growth. This supports the intriguing hypothesis that ECM components may be considered as nutrient sources, primarily under soluble nutrient-depleted conditions.

show abstract

AMPK negatively regulates tensin-dependent integrin activity

Cited by 97 publications

References 65 publications

Talin – the master of integrin adhesions

Talin – the master of integrin adhesions

Energetic adaptations: Metabolic control of endocytic membrane traffic

Extracellular matrix internalization links nutrient signalling to invasive migration

Contact Info

Product

Resources

About