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Drosophila integrin-linked kinase is required at sites of integrin adhesion to link the cytoskeleton to the plasma membrane.

Zervas CG, Gregory SL, Brown NH - J. Cell Biol. (2001)

Bottom Line: Integrin-linked kinase (ILK) was identified by its interaction with the cytoplasmic tail of human beta1 integrin and previous data suggest that ILK is a component of diverse signaling pathways, including integrin, Wnt, and protein kinase B.ILK mutations cause embryonic lethality and defects in muscle attachment, and clones of cells lacking ILK in the adult wing fail to adhere, forming wing blisters.Surprisingly, mutations in the kinase domain shown to inactivate the kinase activity of human ILK do not show any phenotype in Drosophila, suggesting a kinase-independent function for ILK.

View Article: PubMed Central - PubMed

Affiliation: Wellcome/CRC Institute and Department of Anatomy, University of Cambridge, Cambridge CB2 1QR, United Kingdom.

ABSTRACT
Integrin-linked kinase (ILK) was identified by its interaction with the cytoplasmic tail of human beta1 integrin and previous data suggest that ILK is a component of diverse signaling pathways, including integrin, Wnt, and protein kinase B. Here we show that the absence of ILK function in Drosophila causes defects similar to loss of integrin adhesion, but not similar to loss of these signaling pathways. ILK mutations cause embryonic lethality and defects in muscle attachment, and clones of cells lacking ILK in the adult wing fail to adhere, forming wing blisters. Consistent with this, an ILK-green fluorescent protein fusion protein colocalizes with the position-specific integrins at sites of integrin function: muscle attachment sites and the basal junctions of the wing epithelium. Surprisingly, mutations in the kinase domain shown to inactivate the kinase activity of human ILK do not show any phenotype in Drosophila, suggesting a kinase-independent function for ILK. The muscle detachment in ILK mutants is associated with detachment of the actin filaments from the muscle ends, unlike integrin mutants, in which the primary defect is detachment of the plasma membrane from the extracellular matrix. Our data suggest that ILK is a component of the structure linking the cytoskeleton and the plasma membrane at sites of integrin-mediated adhesion.

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Embryos mutant for ILK do not show a cuticle phenotype. Cuticle preparations that show the patterning of the underlying epidermis. Wild-type cuticles (a) are indistinguishable from ILK  mutant [ilk1/DF(3L)Pc-14d] cuticles (b). This is in contrast to  mutations that affect Wnt signaling in the epidermis, such as removal of the β-catenin homologue armadillo (c), which causes a dramatic failure in epidermal patterning.
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Figure 5: Embryos mutant for ILK do not show a cuticle phenotype. Cuticle preparations that show the patterning of the underlying epidermis. Wild-type cuticles (a) are indistinguishable from ILK mutant [ilk1/DF(3L)Pc-14d] cuticles (b). This is in contrast to mutations that affect Wnt signaling in the epidermis, such as removal of the β-catenin homologue armadillo (c), which causes a dramatic failure in epidermal patterning.

Mentions: We found that embryos homozygous for ilk1 die at the end of embryogenesis. To check whether the ilk mutant embryos have defects similar to the pattern defects caused by the loss of the Wnt signal through β-catenin (armadillo) (Peifer et al. 1991), or the reduced cuticle caused by loss of PKB (Perrimon 1996; Staveley et al. 1998), we examined the cuticle secreted by the epidermis. We found that the cuticle of ilk mutant embryos is completely normal (compare Fig. 5, a with b) with, for example, no indication of the dramatic pattern changes observed when β-catenin is defective (c). The development of the midgut was also found to be normal (data not shown), ruling out a requirement for ILK in the β-catenin signaling that occurs in the visceral mesoderm (Yu et al. 1996).


Drosophila integrin-linked kinase is required at sites of integrin adhesion to link the cytoskeleton to the plasma membrane.

Zervas CG, Gregory SL, Brown NH - J. Cell Biol. (2001)

Embryos mutant for ILK do not show a cuticle phenotype. Cuticle preparations that show the patterning of the underlying epidermis. Wild-type cuticles (a) are indistinguishable from ILK  mutant [ilk1/DF(3L)Pc-14d] cuticles (b). This is in contrast to  mutations that affect Wnt signaling in the epidermis, such as removal of the β-catenin homologue armadillo (c), which causes a dramatic failure in epidermal patterning.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2198807&req=5

Figure 5: Embryos mutant for ILK do not show a cuticle phenotype. Cuticle preparations that show the patterning of the underlying epidermis. Wild-type cuticles (a) are indistinguishable from ILK mutant [ilk1/DF(3L)Pc-14d] cuticles (b). This is in contrast to mutations that affect Wnt signaling in the epidermis, such as removal of the β-catenin homologue armadillo (c), which causes a dramatic failure in epidermal patterning.
Mentions: We found that embryos homozygous for ilk1 die at the end of embryogenesis. To check whether the ilk mutant embryos have defects similar to the pattern defects caused by the loss of the Wnt signal through β-catenin (armadillo) (Peifer et al. 1991), or the reduced cuticle caused by loss of PKB (Perrimon 1996; Staveley et al. 1998), we examined the cuticle secreted by the epidermis. We found that the cuticle of ilk mutant embryos is completely normal (compare Fig. 5, a with b) with, for example, no indication of the dramatic pattern changes observed when β-catenin is defective (c). The development of the midgut was also found to be normal (data not shown), ruling out a requirement for ILK in the β-catenin signaling that occurs in the visceral mesoderm (Yu et al. 1996).

Bottom Line: Integrin-linked kinase (ILK) was identified by its interaction with the cytoplasmic tail of human beta1 integrin and previous data suggest that ILK is a component of diverse signaling pathways, including integrin, Wnt, and protein kinase B.ILK mutations cause embryonic lethality and defects in muscle attachment, and clones of cells lacking ILK in the adult wing fail to adhere, forming wing blisters.Surprisingly, mutations in the kinase domain shown to inactivate the kinase activity of human ILK do not show any phenotype in Drosophila, suggesting a kinase-independent function for ILK.

View Article: PubMed Central - PubMed

Affiliation: Wellcome/CRC Institute and Department of Anatomy, University of Cambridge, Cambridge CB2 1QR, United Kingdom.

ABSTRACT
Integrin-linked kinase (ILK) was identified by its interaction with the cytoplasmic tail of human beta1 integrin and previous data suggest that ILK is a component of diverse signaling pathways, including integrin, Wnt, and protein kinase B. Here we show that the absence of ILK function in Drosophila causes defects similar to loss of integrin adhesion, but not similar to loss of these signaling pathways. ILK mutations cause embryonic lethality and defects in muscle attachment, and clones of cells lacking ILK in the adult wing fail to adhere, forming wing blisters. Consistent with this, an ILK-green fluorescent protein fusion protein colocalizes with the position-specific integrins at sites of integrin function: muscle attachment sites and the basal junctions of the wing epithelium. Surprisingly, mutations in the kinase domain shown to inactivate the kinase activity of human ILK do not show any phenotype in Drosophila, suggesting a kinase-independent function for ILK. The muscle detachment in ILK mutants is associated with detachment of the actin filaments from the muscle ends, unlike integrin mutants, in which the primary defect is detachment of the plasma membrane from the extracellular matrix. Our data suggest that ILK is a component of the structure linking the cytoskeleton and the plasma membrane at sites of integrin-mediated adhesion.

Show MeSH
Related in: MedlinePlus