Disease relevance of MIP

• Dominantly inherited cataracts with differing clinical features were found in two families carrying different point mutations in the gene encoding lens water channel protein AQP0 (major intrinsic protein, MIP) [1].
• Osmotically shocked yeast cells were affected only slightly by expression of the Escherichia coli glycerol channel GlpF, which belongs to the MIP family but is a weak water channel [2].
• An invasion assay shows that the MIP protein from Legionella pneumophila (LpMIP), which has an equivalent N-terminal alpha-helix, can substitute for TcMIP [3].
• After 8 weeks, there were fewer activated macrophages in livers of gp91(phox-/-) mice than controls, despite similar mRNA levels for MCP and MIP chemokines, but fibrosis was similar [4].
• The severity of dyspnea expressed as the slope of the relationship between BS and VE/MVV (DBS/D[VE/MVV]) showed in COPD a significant inverse correlation with VC, FEV1, MIP, and a positive correlation with PaCO2 and VE/MVV at rest [5].

Psychiatry related information on MIP

• Although both groups scored high on the Mania Rating Scale, MIP patients had significantly more often been diagnosed as schizophrenic, or anxiety disorders, with long delays to first diagnosis as bipolar disorder [6].
• We tested the hypotheses that those users who develop MAMP-induced psychosis (MIP) have greater familial loading for psychotic disorders than users with no psychosis [7].

High impact information on MIP

• Missense mutations in MIP underlie autosomal dominant 'polymorphic' and lamellar cataracts linked to 12q [8].
• The major intrinsic protein (MIP) of the vertebrate eye lens is the first identified member of a sequence-related family of cell-membrane proteins that appears to have evolved by gene duplication [9].
• Several members of the MIP family transport water (aquaporins), glycerol and other small molecules in microbial, plant and animal cells [9].
• The lens opacity mutation is an amino-acid substitution that inhibits targeting of MIP to the cell-membrane [9].
• The cataract Fraser mutation is a transposon-induced splicing error that substitutes a long terminal repeat sequence for the carboxy-terminus of MIP [9].

Biological context of MIP

• The longest open reading frame of 846 bp encoded a 282-amino-acid hydrophobic protein that contained the conserved NPA motifs of MIP family members [10].
• Using two-color fluorescence in situ hybridization on high-resolution R-banded chromosomes and human genomic DNA clones for AQP2 and MIP as probes, we found that both genes mapped closely within the human chromosome region 12q13 [11].
• Although missense mutations in AQP1 and AQP2 proteins are known to result in recessive traits in vivo and in vitro, when E134G or T138R are co-expressed with wild-type AQP0 protein, the mutant proteins exhibit dominant negative behaviour [1].
• Aquaporin-0 (MIP26) functions to maintain fluid balance in the lens [12].
• To construct a physical map and identify novel aquaporin gene members on this cluster, a human CEPH B yeast artificial chromosome (YAC) library was screened by PCR using primers derived from exon 4 of AQP2 and AQP0 genes [13].

Anatomical context of MIP

• When expressed in Xenopus oocytes, the osmotic water permeability (P(f)) of MIP and AQP2 was 48 and 245 x 10(-)(4) cm/s, respectively [14].
• These allelic cataract mutations provide the first direct evidence that MIP plays a crucial role in the development of a transparent eye lens [9].
• In this paper we demonstrate that this P25 polypeptide is a member of the MIP family of membrane channel proteins, and that P25 forms homotetramers in the native membranes [15].
• Structural analysis of a MIP family protein from the digestive tract of Cicadella viridis [15].
• We show now that MP70 can be solubilized separately from MIP in mild detergent solutions, and that this treatment results in the dissociation of the fibre gap junctions [16].

Associations of MIP with chemical compounds

• Glycerol transporters identified to date belong to the Major Intrinsic Protein (MIP) family of integral membrane proteins, and one of them, aquaporin-3 (AQP3), has been characterized in mammals [17].
• Replacement of the glycine at this site in AQP0, AQP1, and AQP2 blocked expression of the mutants at the oocyte plasma membrane [18].
• CONCLUSIONS: Specific sites of MIP N- and C-terminal cleavage in selenite-induced cataractous lenses were identified [19].
• METHODS: MIP was isolated from single human lenses of various ages (7- 86 years) by homogenization of the lenses, followed by centrifugation and urea washes of the membranes [20].
• Diisopropylphosphorofluoridate (DFP), the phosphate analogue of the phosphoroamidate MIP, was used for comparison [21].

Physical interactions of MIP

• The C terminus of lens aquaporin 0 interacts with the cytoskeletal proteins filensin and CP49 [22].

Regulatory relationships of MIP

• Similarly, the analogous mass shift for aged MIP-inhibited BChE was 122.4 +/- 0.7 Da, corresponding to a monoisopropylphosphoroamido adduct [21].

Other interactions of MIP

• Proteoliposomes containing either AQP1, MIP26, or P25 were injected into Xenopus oocytes [23].
• Moreover, P(f) was stimulated 2.6- and 3.3-fold after helix 5 of AQP1 and AQP4 was spliced into MIP, respectively [14].
• In mammalian cells, more than 10 isoforms (AQP0-AQP10) have been identified so far [24].
• In mammals, there are currently 10 families of water channels, referred to as aquaporins (AQP): AQP0-AQP9 [25].
• Immunoelectron microscopy confirmed that filensin and AQP0 were present in the same membrane compartments [22].

Analytical, diagnostic and therapeutic context of MIP

• Northern blot analysis of MT RNA showed a single transcript of about 1-1.3 kb for Rp-MIP [26].
• The simulations demonstrate that AQP0, in single or double lipid bilayers, is not closed to water transport and that thermal motions of critical side-chains are sufficient to facilitate the movement of water past any of its constriction regions [27].
• For comparison, CD of MIP26 in OG gave 49 +/- 7% alpha-helix and 32 +/- 12% beta-sheet and -turn; FTIR gave 32 +/- 8% alpha-helix and 45 +/- 6% beta-sheet and -turn [28].
• Membrane proteins still embedded in the membranes were digested with trypsin, and the resulting C-terminal peptides of AQP0 were analyzed by HPLC tandem mass spectrometry, permitting the identification of modifications and estimation of their abundance [29].
• CHIP28 (glycosylated and nonglycosylated) and MIP26 were purified further by high-performance size-exclusion chromatography, eluting in OG as apparent dimers and tetramers, respectively [28].

References