Focal adhesion kinase is not required for integrin function or viability in<i>Drosophila</i>

Grabbe, Caroline; Zervas, Christos G.; Hunter, Tony; Brown, Nicholas H.; Palmer, Ruth

doi:10.1242/dev.01462

Cited by 59 publications

(85 citation statements)

References 67 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Animals in a genetically sensitized background, like PINCH Q38A -Flag rescued flies, may serve as a model for assessing the contributions of other non-essential adhesion complex components, like Tensin, Vinculin and FAK, whose functions have been somewhat elusive (Alatortsev et al, 1997;Lee et al, 2003;Grabbe et al, 2004;Torgler et al, 2004). Like RSU-1, these proteins might support integrin function and viability in combination with other adhesion complex components.…”

Section: A Crucial Role For Rsu-1 In Pinch-ilk Complex Functionmentioning

confidence: 99%

A critical role for Ras Suppressor-1 (RSU-1) revealed when PINCH-Integrin-linked Kinase (ILK) binding is disrupted

Elias

Pronovost

Cahill

et al. 2012

Journal of Cell Science

View full text Add to dashboard Cite

Summary PINCH, integrin-linked kinase (ILK) and Ras suppressor-1 (RSU-1) are molecular scaffolding proteins that form a physical complex downstream of integrins, and have overlapping roles in cellular adhesion. In Drosophila, PINCH and ILK colocalize in cells and have indistinguishable functions in maintaining wing adhesion and integrin to actin linkage in the muscle. We sought to determine whether the direct physical interaction between PINCH and ILK was essential for their functions using transgenic flies expressing a version of PINCH with a point mutation that disrupts ILK binding (PINCH Q38A ). We demonstrate that the PINCH-ILK interaction is not required for viability, for integrin-mediated adhesion of the wing or muscle, or for maintaining appropriate localization or levels of either PINCH or ILK. These results suggest alternative modes for PINCH localization, stabilization and linkage to the actin cytoskeleton that are independent of a direct interaction with ILK. Furthermore, we identified a synthetic lethality in flies carrying both the PINCH Q38A mutation and a null mutation in the gene encoding RSU-1. This lethality does not result from PINCH mislocalization or destabilization, and illustrates a novel compensatory role for RSU-1 in maintaining viability in flies with compromised PINCH-ILK binding. Taken together, this work highlights the existence of redundant mechanisms in adhesion complex assembly that support integrin function in vivo.

show abstract

Section: A Crucial Role For Rsu-1 In Pinch-ilk Complex Functionmentioning

confidence: 99%

A critical role for Ras Suppressor-1 (RSU-1) revealed when PINCH-Integrin-linked Kinase (ILK) binding is disrupted

Elias

Pronovost

Cahill

et al. 2012

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Analysis of integrin function in flies is simplified by the fact that there is only one widely expressed -integrin orthologue, PS, encoded by myospheroid (mys). Mutations in more than a dozen genes encoding cytoplasmic factors involved in integrin function have been isolated and characterised in Drosophila, including mutations in the conserved focal adhesion components PINCH (Clark et al, 2003), tensin (Torgler et al, 2004), ILK (Zervas et al, 2001), FAK (Grabbe et al, 2004) and paxillin (Yagi et al, 2001). Moreover, flies have a well-conserved orthologue of talin, encoded by rhea .…”

Section: Introductionmentioning

confidence: 99%

In vivo functional analysis reveals specific roles for the integrin-binding sites of talin

Ellis

Pines

Fairchild

et al. 2011

Journal of Cell Science

View full text Add to dashboard Cite

SummaryAdhesion receptors play diverse roles during animal development and require precise spatiotemporal regulation, which is achieved through the activity of their binding partners. Integrins, adhesion receptors that mediate cell attachment to the extracellular matrix (ECM), connect to the intracellular environment through the cytoplasmic adapter protein talin. Talin has two essential functions: orchestrating the assembly of the intracellular adhesion complex (IAC), which associates with integrin, and regulating the affinity of integrins for the ECM. Talin can bind to integrins through two different integrin-binding sites (IBS-1 and IBS-2, respectively). Here, we have investigated the roles of each in the context of Drosophila development. We find that although IBS-1 and IBS-2 are partially redundant, they each have specialized roles during development: IBS-1 reinforces integrin attachment to the ECM, whereas IBS-2 reinforces the link between integrins and the IAC. Disruption of each IBS has different developmental consequences, illustrating how the functional diversity of integrin-mediated adhesion is achieved.

show abstract

“…We find that activity of the calcium/calmodulin-dependent kinase II (CaMKII) is necessary for glutamate application to activate PI3K, and expression of the constitutively active CaMKII T287D (Jin et al 1998) is sufficient both to activate PI3K even in the absence of glutamate and to confer several other neuronal phenotypes consistent with PI3K hyperactivation. We also find that CaMKII T287D requires the nonreceptor tyrosine kinase DFak for this PI3K activation: the DFak CG1 null mutation (Grabbe et al 2004) blocks the ability of glutamate application to activate PI3K and prevents CaMKII T287D from hyperactivating PI3K. Finally, CaMKII T287D expression completely suppresses the hyperexcitability conferred by the DmGluRA null mutation DmGluRA 112b .…”

mentioning

confidence: 67%

“…Flies carrying the UAS-ala, UAS-CaMKII T287A , and UAS-CaMKII T287D transgenes, which encode a CaMKII inhibitor peptide, calcium/ calmodulin-dependent CaMKII, and calcium/calmodulinindependent CaMKII, respectively (Griffith et al 1994;Park et al 2002), were provided by Leslie C. Griffith (Brandeis University, Waltham, MA). Flies carrying the DFak CG1 deletion mutation and UAS-DFak 1 transgene (Grabbe et al 2004) were provided by Ruth Palmer (Umeå University, Umeå, Sweden). Flies carrying the DmGluRA 112b deletion mutation (Bogdanik et al 2004) were provided by Marie-Laure Parmentier (Unité Propre de Recherche Centre, Montpellier, France).…”

Section: Drosophila Stocksmentioning

confidence: 99%

“…Furthermore, both Pyk2 and Fak are capable of activating PI3K (Chen and Guan 1994;Schlaepfer et al 1994;Guinebault et al 1995;Chen et al 1996;Dikic et al 1996;Avraham et al 2000;Rocic et al 2001;Montiel et al 2007). Two CaMKII phosphorylation sites on Fak, serines 843 and 910, are conserved in DFak, raising the possibility that CaMKII phosphorylates DFak at these serine positions, which leads to DFak and then PI3K activation (Grabbe et al 2004).…”

Section: Camkii Regulates Pi3k Activity In Drosophila Motor Nerve Termentioning

confidence: 99%

See 1 more Smart Citation

The Metabotropic Glutamate Receptor Activates the Lipid Kinase PI3K in Drosophila Motor Neurons Through the Calcium/Calmodulin-Dependent Protein Kinase II and the Nonreceptor Tyrosine Protein Kinase DFak

Lin

Summerville

Howlett³

et al. 2011

Genetics

View full text Add to dashboard Cite

Ligand activation of the metabotropic glutamate receptor (mGluR) activates the lipid kinase PI3K in both the mammalian central nervous system and Drosophila motor nerve terminal. In several subregions of the mammalian brain, mGluR-mediated PI3K activation is essential for a form of synaptic plasticity termed long-term depression (LTD), which is implicated in neurological diseases such as fragile X and autism. In Drosophila larval motor neurons, ligand activation of DmGluRA, the sole Drosophila mGluR, similarly mediates a PI3K-dependent downregulation of neuronal activity. The mechanism by which mGluR activates PI3K remains incompletely understood in either mammals or Drosophila. Here we identify CaMKII and the nonreceptor tyrosine kinase DFak as critical intermediates in the DmGluRA-dependent activation of PI3K at Drosophila motor nerve terminals. We find that transgeneinduced CaMKII inhibition or the DFak CG1 null mutation each block the ability of glutamate application to activate PI3K in larval motor nerve terminals, whereas transgene-induced CaMKII activation increases PI3K activity in motor nerve terminals in a DFakdependent manner, even in the absence of glutamate application. We also find that CaMKII activation induces other PI3K-dependent effects, such as increased motor axon diameter and increased synapse number at the larval neuromuscular junction. CaMKII, but not PI3K, requires DFak activity for these increases. We conclude that the activation of PI3K by DmGluRA is mediated by CaMKII and DFak.

show abstract

Focal adhesion kinase is not required for integrin function or viability inDrosophila

Cited by 59 publications

References 67 publications

A critical role for Ras Suppressor-1 (RSU-1) revealed when PINCH-Integrin-linked Kinase (ILK) binding is disrupted

A critical role for Ras Suppressor-1 (RSU-1) revealed when PINCH-Integrin-linked Kinase (ILK) binding is disrupted

In vivo functional analysis reveals specific roles for the integrin-binding sites of talin

The Metabotropic Glutamate Receptor Activates the Lipid Kinase PI3K in Drosophila Motor Neurons Through the Calcium/Calmodulin-Dependent Protein Kinase II and the Nonreceptor Tyrosine Protein Kinase DFak

Contact Info

Product

Resources

About