Disease relevance of Mip

• The mutant MIP26 protein was also expressed in E. coli and incorporated predominantly into the cytoplasmic membrane [1].
• The initial increase in MP26 and gamma-crystallin mRNAs lead us to conclude that initiation of galactose cataracts appears to support, although for a short time period, both epithelial cell elongation and fiber cell differentiation [2].

High impact information on Mip

• In contrast, epithelial cells stimulated with Wnt after priming with FGF elongated, accumulated beta-crystallin, aquaporin-0, p57kip2, and altered their expression of cadherins [3].
• Because MIP is specifically expressed in lens fiber cells, we investigated in this study the activation of Mip expression after triggering differentiation of rat lens epithelia explants by fibroblast growth factor (FGF)-2 [4].
• Up-regulation of Mip at the transcriptional level was simultaneous with the activation of the FGF down-stream signaling components, ERK1/2 and JNK [4].
• This inhibition pattern was recapitulated in reporter assays for transfection of the rat lens epithelia explants, driven by the Mip promoter (-1648/+44) [4].
• We found transcripts of three of 10 aquaporins in hepatocytes (aquaporin 8 aquaporin 9 > aquaporin 0) by reverse transcription-polymerase chain reaction and quantitative ribonuclease protection assays; immunohistochemistry confirmed the presence of these three proteins in liver [5].

Biological context of Mip

• This study suggests that a microtubule-based motor system exists in the lens and plays an important role in transporting membrane proteins such as aquaporin 0 in the vesicles during fiber cell differentiation and elongation [6].
• We concluded that the ability of AQP0 to arrange itself in micro-domains conferred functional properties that might contribute to the maintenance of lens transparency and homeostasis [7].
• Analysis of the predicted amino acid sequence indicated a hydrophobic protein with 4-6 membrane-spanning domains, with one N-linked glycosylation site, two conserved NPA boxes common to MIP26 family proteins, and conserved residue C189 common to water channels [8].

Anatomical context of Mip

• A membrane signal peptide (PelB) was used for secretion of MIP26 into the cytoplasmic membrane [1].
• The complete cDNA of rat eye lens major intrinsic protein (MIP26) was sequenced using the dideoxy chain termination method [1].
• A 28 kDa sarcolemmal antigen in kidney principal cell basolateral membranes: relationship to orthogonal arrays and MIP26 [9].
• Interestingly, freeze-fracture electron microscopy has shown that characteristic orthogonal arrays of intramembrane particles (OAPs) are found on the basolateral plasma membranes of collecting duct principal cells, and that morphologically identical OAPs present in lens fiber cell plasma membranes contain the protein MIP26 [9].
• This differs from what the authors reported to occur with MP26 mRNA, a fiber cell-specific gene transcript [10].

Associations of Mip with chemical compounds

• MIP26 was extracted with n-octyl beta-D-glucopyranoside and then purified on an affinity gel column [1].
• This was indicated by reduced BrdU incorporation and decreased expression of beta- and gamma-crystallins, MIP26, CP49, and filensin [11].
• We therefore modified the MIP26 molecule using a site-directed mutagenesis method to generate a mutant MIP26 at the appropriate asparagine residue (Asn244-->Asp) near the C-terminus [1].
• These results indicate that the synthesis of lens membrane components is highly coordinated and imply that the plasma membrane accumulates constant proportions of cholesterol, phospholipid, and MP26 throughout the course of fiber cell elongation [12].
• Young rat lenses were incubated with either tritiated water as the substrate for cholesterol and fatty acid synthesis or tritiated leucine as the substrate for MP26 synthesis [12].

Other interactions of Mip

• An homologous cDNA (WCH3) was obtained from rat kidney and found to encode a 276 amino acid, 29 kDa protein with 39% amino acid identity to rat CHIP28, 50% to WCH-CD and 49% to MIP26 [8].

Analytical, diagnostic and therapeutic context of Mip

• Both native and mutant cDNAs coding for rat MIP26 were amplified by PCR and subcloned into the pPOW expression vector for expression of Escherichia coli [1].
• By indirect immunofluorescence, western blotting and northern blotting, MIP26 was found only in lens fibers [9].
• The MP26 was recovered both by immunoprecipitation from each fraction with anti-MP26 polyclonal antibody and from sodium dodecyl sulfate polyacrylamide gel electrophoresis gels of intact crude membrane, which was isolated from lens fractions by dissolving the lens in a urea containing-buffer [12].
• By Northern blot analysis we quantitated the MP26 and gamma-crystallin mRNAs found in the lens at various times spanning from 0 to 96 hr on galactose [2].
• The data was also confirmed by in situ hybridization of various lens sections to both gamma-crystallin and MP26 35S-labeled antisense RNA probes [2].

References