MP20, the second most abundant lens membrane protein and member of the tetraspanin superfamily, joins the list of ligands of galectin-3

Gonen, Tamir; Grey, Angus C.; Jacobs, Marc; Donaldson, Paul J.; Kistler, Joerg

doi:10.1186/1471-2121-2-17

Cited by 36 publications

(8 citation statements)

References 29 publications

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“…MP20, a member of the tetraspanin superfamily, is the most abundant integral membrane protein of lens fiber cells, which appears to be distributed uniformly in the plasma membrane but also occurs in distinct membrane junctional domains early during embryonal development [ 9 , 28 - 30 ].Mutations in MP20 severely disrupt normal crystalline fiber cell arrangement in the lens and cause cataractogenesis [ 7 , 8 , 31 ]. Tetraspanins form contacts with other cells or the extracellular matrix by binding to other tetraspanins, to adhesion receptors such as integrins, and to extracellular proteins [ 32 - 34 ]; in this context, recently MP20 and galectin-3 were identified to co-localize in selected areas of the cell plasma membrane and biochemical analysis confirmed that MP20 and galectin-3 interact with each other [ 11 ]. In fact, galectin-3 is a multifunctional protein, which occurs early during embryonal development, with reported involvement in development, oncogenesis, and inflammation [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…It encodes an abundant integral lens membrane protein MP20 which is a new regulatory protein important for mammalian lens fiber cell junctional formation [ 9 ]. Lens-specific MP20 is classified as a member of the PMP22/EMP/MP20 subfamily of tetraspanins [ 10 ] and adds to a growing list of ligands of galectin-3[ 11 ], a known adhesion modulator that is expressed by microglial cells of adult brain [ 12 ] and contributes to injury in the deep gray matter areas of the brain [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Absence of mutations in four genes encoding for congenital cataract and expressed in the human brain in Tunisian families with cataract and mental retardation

et al. 2011

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BackgroundTo identify the genetic defect associated with autosomal recessive congenital cataract (ARCC), mental retardation (MR) and ARCC, MR and microcephaly present in most patients in four Tunisian consanguineous families.MethodsWe screened four genes implicated in congenital cataract by direct sequencing in two groups of patients; those affected by ARCC associated to MR and those who presented also microcephaly. Among its three genes PAX6, PITX3 and HSF4 are expressed in human brain and one gene LIM2 encodes for the protein MP20 that interact with the protein galectin-3 expressed in human brain and plays a crucial role in its development. All genes were screened by direct sequencing in two groups of patients; those affected by ARCC associated to MR and those who presented also microcephaly.ResultsWe report no mutation in the four genes of congenital cataract and its flanking regions. Only variations that did not segregate with the studied phenotypes (ARCC associated to MR, ARCC associated with MR and microcephaly) are reported. We detected three intronic variations in PAX6 gene: IVS4 -274insG (intron 4), IVS12 -174G>A (intron12) in the four studied families and IVS4 -195G>A (intron 4) in two families. Two substitutions polymorphisms in PITX3 gene: c.439 C>T (exon 3) and c.930 C>A (exon4) in one family. One intronic variation in HSF4 gene: IVS7 +93C>T (intron 7) identified in one family. And three intronic substitutions in LIM2 gene identified in all four studied families: IVS2 -24A>G (intron 2), IVS4 +32C>T (intron 4) and c.*15A>C (3'-downstream sequence).ConclusionAlthough the role of the four studied genes: PAX6, PITX3, HSF4 and LIM2 in both ocular and central nervous system development, we report the absence of mutations in all studied genes in four families with phenotypes associating cataract, MR and microcephaly.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Absence of mutations in four genes encoding for congenital cataract and expressed in the human brain in Tunisian families with cataract and mental retardation

et al. 2011

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“…Lim2 is present throughout the lens fibre membrane [70,71], where it is believed to interact with galectin 3 [72], a known facilitator and modulator of cellular adhesion [73]. Finally, in mice deficient in Lim2, the fibre mass is readily dissociated into individual cells [62], suggesting a defect in intercellular adhesion (see also figure 8).…”

Section: Intercellular Junctions and Adhesion Proteinsmentioning

confidence: 99%

“…The notion that Lim2 could also be an adhesive protein is based on the recognition that Lim2 is a member of a family of adhesion-related proteins that includes claudins and peripheral myelin protein 22 [62]. Lim2 is present throughout the lens fibre membrane [70,71], where it is believed to interact with galectin 3 [72], a known facilitator and modulator of cellular adhesion [73]. Finally, in mice deficient in Lim2, the fibre mass is readily dissociated into individual cells [62], suggesting a defect in intercellular adhesion (see also figure 8).…”

Section: Intercellular Junctions and Adhesion Proteinsmentioning

confidence: 99%

Biological glass: structural determinants of eye lens transparency

Bassnett

Shi

Vrensen

2011

Phil. Trans. R. Soc. B

271

258

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The purpose of the lens is to project a sharply focused, undistorted image of the visual surround onto the neural retina. The first pre-requisite, therefore, is that the tissue should be transparent. Despite the presence of remarkably high levels of protein, the lens cytosol remains transparent as a result of short-range-order interactions between the proteins. At a cellular level, the programmed elimination of nuclei and other light-scattering organelles from cells located within the pupillary space contributes directly to tissue transparency. Scattering at the cell borders is minimized by the close apposition of lens fibre cells facilitated by a plethora of adhesive proteins, some expressed only in the lens. Similarly, refractive index matching between lens membranes and cytosol is believed to minimize scatter. Refractive index matching between the cytoplasm of adjacent cells is achieved through the formation of cellular fusions that allow the intermingling of proteins. Together, these structural adaptations serve to minimize light scatter and enable this living, cellular structure to function as 'biological glass'.

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“…Therefore, the reported urea-induced destabilization of the AMPA-R is a phenomenon observed in a very specific experimental system. It is important to note that 4 M urea wash of the membrane is an effective approach in improving the purity and quality of other membrane proteins, such as gap junction connexins and aquaporins [ 100 – 102 ]. In addition, vesicles that were washed with KI maintain their ability to bind to molecular motors and thus can be used for in vitro motility assays, suggesting that motor acceptors on the vesicles are unaffected by the KI wash [ 103 ].…”

Section: Biochemistry Of Endogenous Ampa Receptorsmentioning

confidence: 99%

The Biochemistry, Ultrastructure, and Subunit Assembly Mechanism of AMPA Receptors

Nakagawa

2010

Mol Neurobiol

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The AMPA-type ionotropic glutamate receptors (AMPA-Rs) are tetrameric ligand-gated ion channels that play crucial roles in synaptic transmission and plasticity. Our knowledge about the ultrastructure and subunit assembly mechanisms of intact AMPA-Rs was very limited. However, the new studies using single particle EM and X-ray crystallography are revealing important insights. For example, the tetrameric crystal structure of the GluA2cryst construct provided the atomic view of the intact receptor. In addition, the single particle EM structures of the subunit assembly intermediates revealed the conformational requirement for the dimer-to-tetramer transition during the maturation of AMPA-Rs. These new data in the field provide new models and interpretations. In the brain, the native AMPA-R complexes contain auxiliary subunits that influence subunit assembly, gating, and trafficking of the AMPA-Rs. Understanding the mechanisms of the auxiliary subunits will become increasingly important to precisely describe the function of AMPA-Rs in the brain. The AMPA-R proteomics studies continuously reveal a previously unexpected degree of molecular heterogeneity of the complex. Because the AMPA-Rs are important drug targets for treating various neurological and psychiatric diseases, it is likely that these new native complexes will require detailed mechanistic analysis in the future. The current ultrastructural data on the receptors and the receptor-expressing stable cell lines that were developed during the course of these studies are useful resources for high throughput drug screening and further drug designing. Moreover, we are getting closer to understanding the precise mechanisms of AMPA-R-mediated synaptic plasticity.

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MP20, the second most abundant lens membrane protein and member of the tetraspanin superfamily, joins the list of ligands of galectin-3

Cited by 36 publications

References 29 publications

Absence of mutations in four genes encoding for congenital cataract and expressed in the human brain in Tunisian families with cataract and mental retardation

Absence of mutations in four genes encoding for congenital cataract and expressed in the human brain in Tunisian families with cataract and mental retardation

Biological glass: structural determinants of eye lens transparency

The Biochemistry, Ultrastructure, and Subunit Assembly Mechanism of AMPA Receptors

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