Dataset Information

?- and ?-crystallins modulate the head group order of human lens membranes during aging.

ABSTRACT:

Purpose

To examine the physical properties of human lens cell membranes as a function of age.

Methods

The environment of the phospholipid head groups in fiber cell membranes from human lenses, aged 22 to 83 years, was assessed with Laurdan and two-photon confocal microscopy. The effect of mild thermal stress on head group order was studied with lens pairs in which one intact lens was incubated at 50 °C. Dihydrosphingomyelin vesicles were preloaded with Laurdan, ?-, ?-, or ?-crystallin was added, and surface fluidity was determined.

Results

The membrane head group environment became more fluid with age as indicated by increased water penetration. Furthermore, these changes could be replicated simply by exposing intact human lenses to mild thermal stress; conditions which decreased the concentration of soluble ?- and ?-crystallins. Vesicle binding experiments showed that ?- and ?-, but not ?-, crystallins markedly affected head group order.

Conclusions

The physical properties of cell membranes in the lens nucleus change substantially with age, and ?- and ?-crystallins may modulate this effect. ?-Crystallins may therefore play a role in lens cells, and cells of other tissues, apart from being simple structural proteins. Age-dependent loss of these crystallins may affect membrane integrity and contribute to the dysfunction of lenses in older people.

SUBMITTER: Zhu X

PROVIDER: S-EPMC3066618 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Publications

α- and β-crystallins modulate the head group order of human lens membranes during aging.

Zhu Xiangjia X Gaus Katharina K Lu Yi Y Magenau Astrid A Truscott Roger J W RJ Mitchell Todd W TW

Investigative ophthalmology & visual science 20100519 10

<h4>Purpose</h4>To examine the physical properties of human lens cell membranes as a function of age.<h4>Methods</h4>The environment of the phospholipid head groups in fiber cell membranes from human lenses, aged 22 to 83 years, was assessed with Laurdan and two-photon confocal microscopy. The effect of mild thermal stress on head group order was studied with lens pairs in which one intact lens was incubated at 50 °C. Dihydrosphingomyelin vesicles were preloaded with Laurdan, α-, β-, or γ-crysta ...[more]

PMID: 20484582

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Project description:Crystallins are transparent, refractive proteins that contribute to the focusing power of the vertebrate eye lens. These proteins are extremely soluble and resist aggregation for decades, even under crowded conditions. Crystallins have evolved to avoid strong interprotein interactions and have unusual hydration properties. Crystallin aggregation resulting from mutation, damage, or aging can lead to cataract, a disease state characterized by opacity of the lens.Different aggregation mechanisms can occur, following multiple pathways and leading to aggregates with varied morphologies. Studies of variant proteins found in individuals with childhood-onset cataract have provided insight into the molecular factors underlying crystallin stability and solubility. Modulation of exposed hydrophobic surface is critical, as is preventing specific intermolecular interactions that could provide nucleation sites for aggregation. Biophysical measurements and structural biology techniques are beginning to provide a detailed picture of how crystallins crowd into the lens, providing high refractivity while avoiding excessively tight binding that would lead to aggregation.Despite the central biological importance of refractivity, relatively few experimental measurements have been made for lens crystallins. Our work and that of others have shown that hydration is important to the high refractive index of crystallin proteins, as are interactions between pairs of aromatic residues and potentially other specific structural features.This Account describes our efforts to understand both the functional and disease states of vertebrate eye lens crystallins, particularly the ?-crystallins. We use a variety of biophysical techniques, notably NMR spectroscopy, to investigate crystallin stability and solubility. In the first section, we describe efforts to understand the relative stability and aggregation propensity of different ?S-crystallin variants. The second section focuses on interactions of these proteins with the holdase chaperone ?B-crystallin. The third, fourth, and fifth sections explore different modes of aggregation available to crystallin proteins, and the final section highlights the importance of refractive index and the sometimes conflicting demands of selection for refractivity and solubility.