Disease relevance of IFT74

• Mutations in the gene encoding capillary morphogenesis protein 2 cause juvenile hyaline fibromatosis and infantile systemic hyalinosis [1].
• The protective antigen (PA) protein binds to receptors, either tumor endothelial cell marker 8 (TEM8) or CMG2 (capillary morphogenesis protein 2), and orchestrates the delivery of the lethal and edema factors into the cytosol [2].
• Of interest, CMG2 also functions as a cellular receptor for anthrax toxin [1].
• By contrast, the substitution N657Q significantly reduced toxicity to TEM8 but not CMG2-overexpressing CHO cells [2].
• To extend prior work on targeting of tumor with modified anthrax toxins, we used phage display to select PA variants that preferentially bind to TEM8 as compared with CMG2 [2].

High impact information on IFT74

• How does extracellular matrix control capillary morphogenesis [3]?
• A role for sialyl Lewis-X/A glycoconjugates in capillary morphogenesis [4].
• We report here that antibody directed against the bovine E-selectin inhibited capillary formation, suggesting that in addition to its role in leukocyte adhesion to endothelium, a form of E-selectin is involved in capillary morphogenesis [4].
• We hypothesized that TSP1 might play a role in the inhibition of capillary morphogenesis during the endometrial cycle and examined its expression in 46 human endometrial specimens [5].
• We identified primary cilia and centrosomes in cultured human umbilical vein endothelial cells (HUVEC) by antibodies to acetyl-alpha-tubulin and capillary morphogenesis gene-1 product (CMG-1), a human homologue of the intraflagellar transport (IFT) protein IFT-71 in Chlamydomonas [6].

Chemical compound and disease context of IFT74

• Selection of Anthrax Toxin Protective Antigen Variants That Discriminate between the Cellular Receptors TEM8 and CMG2 and Achieve Targeting of Tumor Cells [2].
• We hypothesized that exposure of mice to severe hypoxia would promote the expression of genes involved in capillary morphogenesis and glucose over fatty acid metabolism in active or disused soleus muscle of mice [7].

Biological context of IFT74

• Differential gene expression during capillary morphogenesis in 3D collagen matrices: regulated expression of genes involved in basement membrane matrix assembly, cell cycle progression, cellular differentiation and G-protein signaling [8].
• Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD [9].
• CONCLUSION: Confirmation of the pathogenicity of IFT74 sequence variants will require screening of other chromosome 9p-linked families [9].
• Mutation screening of CMG2 demonstrated that the siblings were homozygous for a pathogenic missense mutation, V386F [10].
• Binding stoichiometry and kinetics of the interaction of a human anthrax toxin receptor, CMG2, with protective antigen [11].

Anatomical context of IFT74

• In this communication, we examined the expression of mRNA transcripts of TEM8 and CMG2 in primary human and mouse macrophages and mouse tissues by standard and quantitative real-time RT-PCR [12].
• Our results indicate that CMG2 transcripts are preferentially expressed over TEM8 transcripts in primary human and mouse macrophages as compared to immortalized cell lines [12].
• Under LSS, all primary cilia disassembled, and centrosomes were deprived of CMG-1 [6].
• CMG-1 was present in particles along primary cilia of HUVEC at interphase and around the oldest basal body/centriole at interphase and mitosis [6].
• Capillary morphogenesis is a crucial angiogenic response of endothelial cells [13].

Associations of IFT74 with chemical compounds

• Capillary morphogenesis protein-2 is an integrin-like cell surface receptor for laminins and type IV collagen, and may play a key role in cell-matrix or cell-cell interactions [14].
• Actinomycin D and cycloheximide inhibited Shh-induced capillary morphogenesis [15].
• Sonic hedgehog induces capillary morphogenesis by endothelial cells through phosphoinositide 3-kinase [15].
• Shh-induced capillary morphogenesis was also blocked by LY294002, a phosphoinositide 3-kinase (PI3-kinase) inhibitor [15].
• Many serine proteases play important regulatory roles in complex biological systems, but only a few have been linked directly with capillary morphogenesis and angiogenesis [16].

Regulatory relationships of IFT74

• Expression of kinase-inactive c-Fes failed to demonstrate dominant negative effect on VEGF-A-induced chemotaxis and capillary morphogenesis [17].
• Antibodies against the relevant kallikreins on normal endothelial cells revealed that while kallikreins 9, 11, and 12 induced cell growth, only kallikrein 12 regulated invasion and capillary morphogenesis [18].
• ECM components such as fibronectin may influence capillary morphogenesis by the generation of fragments that can modulate proliferation, migration, and protease activation [19].
• Homeobox B3 promotes capillary morphogenesis and angiogenesis [20].

Other interactions of IFT74

• Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor [21].
• Crystal structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor [22].
• Aggressive tumorigenicity correlated with good viability plus capillary morphogenesis on serum starvation and high cyclin D1 expression [23].
• Here we examined the role of VEGF signaling in FGF-2-induced capillary morphogenesis by murine brain capillary endothelial cells (IBE cells) and human umbilical vein endothelial cells [13].
• Moreover, we observed that in our system the EGF receptor was always activated independently of the interstitial flow, and, in addition, the EGF receptor inhibitors used above reduced the phosphorylation state of the receptor, correlating with inhibition of capillary morphogenesis [24].

Analytical, diagnostic and therapeutic context of IFT74

• Its down-regulation, both in a model of capillary morphogenesis and in an animal model of stroke, render it a candidate gene, which may be involved in the regulation of capillary growth, angiogenesis, and in the pathophysiology of stroke [25].
• Angiogenesis of target normal human microvascular endothelial cells (H-MVECs) was assayed by Matrigel invasion, cell proliferation, and capillary morphogenesis. uPAR cleavage and MMP-12 activity were evaluated by western blotting [26].
• India ink perfusion coupled with endothelial cell-specific histochemistry showed that nearly all the neovessels in all wounds were functional, indicating rapid capillary morphogenesis [27].
• AIM: To globally compare the gene expression profiles during the capillary morphogenesis of human microvascular endothelial cells (HMVECs) in an in vitro angiogenesis system with affymetrix oligonucleotide array [28].
• Furthermore, BxPC-3 cell culture supernatants induced endothelial cell capillary morphogenesis in vitro and neovascularization in vivo [29].

References