Disease relevance of betaInt-nu

• Integrin alpha(V)beta(3) mediates diverse responses in vascular cells, ranging from cell adhesion, migration, and proliferation to uptake of adenoviruses [1].
• Soluble alpha 3 beta1 integrin also bound to invasin, a bacterial surface protein, that mediates entry of Yersinia species into the eukaryotic host cell [2].
• Recently we demonstrated that lipopolysaccharide promotes activation of the Ras/mitogen-activated protein cascade in hemocytes and that phagocytosis of Escherichia coli by insect hemocytes is mediated by an integrin-dependent process [Foukas et al. (1998) J. Biol. Chem. 273, 14813--14818] [3].
• The integrin beta subunit is phosphorylated following Rous sarcoma virus transformation [4].

Psychiatry related information on betaInt-nu

• Integrin-mediated short-term memory in Drosophila [5].

High impact information on betaInt-nu

• Attachment, spreading, and growth of myoblasts and neurons on the laminin substrate utilized different binding proteins and were independent of integrin [6].
• We report the characterization of a chromosomal integrin gene that encodes the Drosophila PS2 alpha subunit [7].
• Developmentally regulated alternative splicing of Drosophila integrin PS2 alpha transcripts [7].
• We establish that the position-specific antigen 2 (PS2), a Drosophila cell surface glycoprotein complex, is an invertebrate member of the vertebrate fibronectin receptor (integrin) family [8].
• Volado mutants display impaired olfactory memories within 3 min of training, indicating that the integrin is required for short-term memory processes [5].

Chemical compound and disease context of betaInt-nu

• To determine the role of affinity modulation of alpha(V)beta(3), a novel monovalent ligand-mimetic antibody (WOW-1) was created by replacing the heavy chain hypervariable region 3 of PAC1 Fab with a single alpha(V) integrin-binding domain from multivalent adenovirus penton base [1].

Biological context of betaInt-nu

• Consistent with its expression, removal of betanu only enhanced the phenotype of betaPS in the developing midgut [9].
• Two integrin beta subunits are encoded in the Drosophila genome [9].
• Despite the differences in bodyplan and developmental strategy, integrin adhesion to the extracellular matrix is required for similar processes: the formation of the link that translates muscle contraction into movement of the exoskeleton, cell migration, and morphogenetic interactions between epithelia [10].
• Cell-cell adhesion via the ECM: integrin genetics in fly and worm [10].
• Other integrin functions, such as regulation of gene expression, have not yet been experimentally demonstrated in both organisms [10].

Anatomical context of betaInt-nu

• In embryos lacking the zygotic contribution of betaPS, loss of betanu resulted in enhanced separation between the midgut and the surrounding visceral mesoderm [9].
• The second betasubunit, betanu, is a divergent integrin expressed primarily in the midgut endoderm [9].
• An integrin chicken and egg problem: which comes first, the extracellular matrix or the cytoskeleton [11]?
• Analysis of integrin function in the developing embryos of worms and flies suggests that, although the extracellular matrix directs integrins to organise intracellular proteins, the cytoskeleton may have the first word [11].
• Chemokines guide lymphocytes from blood to secondary lymphoid organs by triggering integrin-dependent firm adhesion under vascular flow and directed migration of T and B lymphocytes within lymphoid tissue [12].

Associations of betaInt-nu with chemical compounds

• This 255 x 10(3) M(r) polypeptide contains the potential integrin recognition sequence Arg-Gly-Asp (RGD) and 16 repeats of a novel 73-77 amino acid motif [13].
• The results provide evidence that integrin-talin adhesion complexes are necessary to maintain tracheal terminal branches and luminal organization [14].
• Furthermore, this activity is calcium-sensitive and is regulated in the EDTA-stabilized conformation of the integrin [15].
• The leucine substitution by proline was shown to affect a residue, which was precisely conserved in different human, rodent, and drosophila integrin-beta polypeptides, and consequently disrupts the alpha-helix formation of the polypeptide segment as determined by Garnier alpha-helicity plot [16].
• Integrin-linked kinase (ILK) is a focal adhesion serine/threonine protein kinase that is emerging as a key signaling protein functioning at one of the early convergence points of integrin- and growth factor-signaling pathways [17].

Physical interactions of betaInt-nu

• We demonstrate that Drosophila PINCH and ILK are complexed in vivo and are coincident at the integrin-rich muscle-attachment sites in embryonic muscle [18].
• Tensin stabilizes integrin adhesive contacts in Drosophila [19].
• Integrin mutants interact with bs mutants to increase the frequency of intervein blisters but do not typically enhance vein defects [20].
• Thus, the struthio gene encodes a putative RNA-binding protein that appears to regulate some aspects of Drosophila integrin functioning [21].

Regulatory relationships of betaInt-nu

• Altogether, these results lead to a model in which integrin-mediated adhesion plays a role in regulating tendon cell differentiation by modulating the activity of the Egfr pathway at the level of its ligand Vein [22].
• The integrin effector PINCH regulates JNK activity and epithelial migration in concert with Ras suppressor 1 [23].
• Kakapo is strongly expressed late during embryogenesis at the most prominent site of position-specific integrin adhesion, the muscle attachment sites [24].
• Collectively, binding of FN to its alpha(5)beta(1) integrin activates a signal transduction pathway that results in the transcriptional activation of the alpha(5) gene likely through altering the phosphorylation state of Sp1 [25].
• These data indicate that the Drosophila integrin cascade triggered by the interaction between BG2-c6 and laminin was initiated at the integrin cluster with tyrosine-phosphorylated proteins, similar to the observations in vertebrate cells [26].

Other interactions of betaInt-nu

• However, we could observe betanu function in the absence of betaPS [9].
• Having generated the tools to eliminate integrin function completely, we confirm that Drosophila integrins do not control proliferation as they do in mammals, and have identified alphaPS3 as a heterodimeric partner for betanu [9].
• Thus, another integrin in addition to PS1 appears to function on the dorsal wing surface [27].
• Moreover, Fak56D genetically interacts with myospheroid, which encodes an integrin beta subunit [28].
• The integrin-linked kinase, ILK, is also essential for integrin function [18].

Analytical, diagnostic and therapeutic context of betaInt-nu

• We have used the polymerase chain reaction to identify a novel integrin receptor beta subunit in Drosophila melanogaster [29].
• Time-lapse and transmission electron microscopy analyses suggest that Wb facilitates integrin-dependent contact over a large surface and controls the cellular behavior of the wing cells, including their exploratory filopodial activity [30].
• Cell culture consisting of Drosophila BG2-c6 cells and laminin revealed its value for the analysis of the integrin-mediated activity of extracellular matrix (Takagi, Y., et al. (1998) Neurosci. Lett. 244, 149-152) [31].
• Integrin-ligand interactions are now considered to provide physical support for cells in order to maintain cohesion, to permit the generation of traction forces to enable movement, and to organize signalling complexes to modulate differentiation and cell fate [32].
• By immunoblotting with antibodies raised towards a synthetic peptide corresponding to a part of the cytoplasmic region of the deduced protein sequence, it was shown that the integrin is present in the membrane of the hemocytes [33].

References