This chapter reviews the biological roles of two members of the small heat shock protein family, HspB4 (α A-crystallin) and HspB5 (α B-crystallin), in lens development, function, and disease. HspB4 and HspB5 are cytoplasmic, structural proteins that are essential for the optical properties of the lens. While the lens continues to grow throughout life, the bulk of the lens is composed of fiber cells that lack the cellular machinery for protein turnover. Thus, lens proteins must remain stable during a full lifespan in order to keep the lens transparent and competent for sight. The α-crystallins have been found to help maintain lens transparency by creating the proper refractive index in the lens that is necessary to refract light onto the retina. The crystallins are divided into two distinct classes, the α-crystallins and the βγ-crystallins, which comprise at least 16 different mammalian crystallin polypeptides that make up 90% of the water-soluble proteins in the lens. Most crystallins appear to be essential for lens transparency, raising the question of why so many different crystallins are required. This question may be partially answered by recent advances in the understanding of HspB4 and HspB5, α-crystallins. HspB4 and HspB5 have the chaperone-like property of binding unfolded proteins, allowing them to act as a sink to trap denatured proteins. This prevents unfolded protein aggregation which can reduce lens transparency and cause age-related lens damage. In addition, the study of mice harboring targeted deletions or mutations of the α-crystallin genes has demonstrated that the α-crystallins are required for lens development and function. In the past two decades, our understanding of α-crystallins structure and function has increased exponentially. Here we review the recent knowledge of the roles of HspB4 and HspB5 in the development of cataracts, the most common cause of blindness. This chapter will outline the current research and the critical goals of future research on α-crystallin functions in cataract disease.
|Title of host publication||Small Stress Proteins and Human Diseases|
|Publisher||Nova Science Publishers, Inc.|
|Number of pages||18|
|State||Published - Dec 1 2011|