Disease relevance of Magi1

• Moreover, mice and nonhuman primates vaccinated with formaldehyde-treated, thermally inactivated virions produce antibodies capable of neutralizing heterologous strains of HIV in peripheral blood mononuclear cell-, MAGI cell-, and U87-based infectivity assays [1].
• Only Magi 6 did not compete with the scorpion toxin LqhalphaIT in binding to site 3 despite high toxicity on lepidoptera larvae of 3.1 nmol/g. The K(i)s of other toxins were between 50 pM for Magi 4 and 1747 nM for Magi 1 [2].

High impact information on Magi1

• These findings suggest that JAM4 together with MAGI-1 provides an adhesion machinery at tight junctions, which may regulate the permeability of kidney glomerulus and small intestinal epithelial cells [3].
• MAGI-1 is a membrane-associated guanylate kinase protein at tight junctions in epithelial cells [3].
• MAGI-1 strengthened JAM4-mediated cell adhesion in L cells and sealing effects in CHO cells [3].
• MAGI-1, ZO-1, and occludin were recruited to JAM4-based cell contacts [3].
• JAM4 and MAGI-1 interacted with each other and formed clusters in COS-7 cells when coexpressed [3].

Biological context of Magi1

• In this report, we describe the cDNA cloning and subcellular distribution of MAGI-1, a MAGUK with three unique structural features: 1) the GuK domain is at the NH2 terminus, 2) the SH3 domain is replaced by two WW domains, and 3) it contains five PDZ domains [4].
• Because we have previously observed MAGI-1 expression in glomerular visceral epithelial cells (podocytes) of the kidney, we screened a glomerular cDNA library to identify the potential binding partners of MAGI-1 and isolated a partial cDNA encoding a novel protein [5].
• Scanning the BPV-1 genome for potential binding sequences, an intragenic AP-1 site (BAP-1) within the E7 open reading frame was detected [6].
• Moreover, the amino acid sequence of Magi 4, which was revealed by cloning of its cDNA, displays similarities to the Na+ channel modifier delta-atracotoxin from the Australian spider Atrax robustus (Hexathelidae) [2].
• In addition, only Magi 5 binds to both site 3 in insects (K(i)=267 nM) and site 4 in rat brain synaptosomes (K(i)=1.2 nM), whereas it showed no affinities for either mammal binding site 3 or insect binding site 4 [2].

Anatomical context of Magi1

• JAM4, a junctional cell adhesion molecule interacting with a tight junction protein, MAGI-1 [3].
• We found MAGI-1 to be associated with cell-cell contacts in human umbilical vein endothelial cells (HUVECs) and in mouse endothelium, where it colocalizes with ESAM [7].
• The membrane-associated guanylate kinase protein, MAGI-1, has been shown to be a component of epithelial tight junctions in both Madin-Darby canine kidney cells and in intestinal epithelium [5].
• The study using a stable transformant of Madine Darby canine kidney (MDCK) cells expressing GFP-Carom revealed that Carom was partially overlapped by MAGI-1 in MDCK cells, which have not yet established mature cell junctions, but became separated from MAGI-1 and colocalized with CASK in polarized cells [8].
• In ileum, however, MAGI-1 was localized at TJs where JAM4 was not detected [9].

Associations of Magi1 with chemical compounds

• MAGI-1 and CASK are membrane-associated guanylate kinases of epithelial junctions [8].
• In proteinuric podocytes, the expression of JAM4 was distinct from that of MAGI-1 or other slit diaphragm molecules such as nephrin and ZO-1 [10].
• Treatment with the gap junction blocker 18beta-glycyrrhetinic acid did not affect expression of MAGI-1 and JAM-1 in Cx32 transfectants [11].

Other interactions of Magi1

• High expression of MAGI-1 in Cx32 transfectants was confirmed by Western blotting and RT-PCR [11].

Analytical, diagnostic and therapeutic context of Magi1

• Immunofluorescence studies of adult kidney revealed that MAGI-1 is expressed in the glomerulus of the kidney, in a manner that parallels the expression of the podocyte-specific protein glomerular epithelial protein 1 [12].
• In cDNA microarray analysis, a 2.5-fold increase in expression of membrane-associated guanylate kinase with inverted orientation-1 (MAGI-1), which is known to be localized at adherens and tight junction regions, was observed [11].

References