8.A.172. The α-Crystallin Chaperone (CryA) Family Lens epithelial cells are the parental cells responsible for growth and development of the transparent ocular lens. Factors that initiate and regulate lens epithelial cell differentiation have been well characterized (Andley 2008). They serve key transport and cell maintenance functions and are the primary source of metabolic activity in the lens. The molecular chaperones, the α-crystallins, are abundant proteins. Besides their important roles in the refractive and light focusing properties of the lens, alpha-crystallins have been implicated in a number of non-refractive pathways including those involving stress response, apoptosis and cell survival. Evidence for their importance in the lens epithelium resulted from studies on the properties of lens epithelial cells from alphaA and alphaB-crystallin gene knockout mice (Andley 2008). Among the transport proteins known to depend on α-crystallins are the Na⁺ channel, Nav1.5 (Nguyen et al. 2021), mitochondrial electron transport (Alam et al. 2020), amyloid-beta aggregation (Ren et al. 2020), members of the TREK‑TRAAK K2P channel family (including TREK‑1, TREK‑2 and TRAAK) (Huang et al. 2018), the Wilson Disease copper ATPase, ATP7B, (Allocca et al. 2018), the muscle calcium ATPase, SERCA (Dremina et al. 2012), and many others.
References:
Alam, S., C.S. Abdullah, R. Aishwarya, M. Morshed, S.S. Nitu, S. Miriyala, M. Panchatcharam, C.G. Kevil, A.W. Orr, and M.S. Bhuiyan. (2020). Dysfunctional Mitochondrial Dynamic and Oxidative Phosphorylation Precedes Cardiac Dysfunction in R120G-αB-Crystallin-Induced Desmin-Related Cardiomyopathy. J Am Heart Assoc 9: e017195.
Allocca, S., M. Ciano, M.C. Ciardulli, C. D''Ambrosio, A. Scaloni, D. Sarnataro, M.G. Caporaso, M. D''Agostino, and S. Bonatti. (2018). An αB-Crystallin Peptide Rescues Compartmentalization and Trafficking Response to Cu Overload of ATP7B-H1069Q, the Most Frequent Cause of Wilson Disease in the Caucasian Population. Int J Mol Sci 19:.
Andley, U.P. (2008). The lens epithelium: focus on the expression and function of the α-crystallin chaperones. Int J Biochem. Cell Biol. 40: 317-323.
Dremina, E.S., V.S. Sharov, and C. Schöneich. (2012). Heat-shock proteins attenuate SERCA inactivation by the anti-apoptotic protein Bcl-2: possible implications for the ER Ca²⁺-mediated apoptosis. Biochem. J. 444: 127-139.
Huang, H., H. Li, K. Shi, L. Wang, X. Zhang, and X. Zhu. (2018). TREK‑TRAAK two‑pore domain potassium channels protect human retinal pigment epithelium cells from oxidative stress. Int J Mol Med 42: 2584-2594.
Nguyen, L.K.C., A. Shimizu, J.E.C. Soh, M. Komeno, A. Sato, and H. Ogita. (2021). Transmembrane protein 168 mutation reduces cardiomyocyte cell surface expression of Nav1.5 through αB-crystallin intracellular dynamics. J Biochem. [Epub: Ahead of Print]
Reddy, V.S. and G.B. Reddy. (2015). Emerging role for αB-crystallin as a therapeutic agent: pros and cons. Curr Mol Med 15: 47-61.
Ren, Z., Z. Dong, P. Xie, J. Lv, Y. Hu, Z. Guan, C. Zhang, and W. Yu. (2020). PNU282987 inhibits amyloid‑β aggregation by upregulating astrocytic endogenous αB‑crystallin and HSP‑70 via regulation of the α7AChR, PI3K/Akt/HSF‑1 signaling axis. Mol Med Rep 22: 201-208.
Thornell, E. and A. Aquilina. (2015). Regulation of αA- and αB-crystallins via phosphorylation in cellular homeostasis. Cell Mol Life Sci 72: 4127-4137.
Examples:
TC#	Name	Organismal Type	Example
8.A.172.1.1	α-Crystallin B chain, CryAB, CryA2, HSPB5, of 175 aas. It has chaperone-like activity and contributes to the transparency and refractive index of the lens. It preventes aggregation of various proteins under a wide range of stress conditions (Andley 2008).		CryAB of Homo sapiens

8.A.172.1.2	αA-Crystallin, CryAA, CryA2, HSPB5, or αBC, of 175 aas and probably 0 TMSs. Both crystallins are regulated by phosphorylation (Thornell and Aquilina 2015). It is a member of the small heat-shock protein family of proteins that respond to various stressful conditions. αBC also is found outside the lens in various non-ocular tissues and acts as a molecular chaperone by preventing aggregation of proteins, inhibits apoptosis and inflammation, and maintains cytoskeletal architecture (Reddy and Reddy 2015).		CryAA of Homo sapiens

8.A.172.1.3	Uncharacterized protein of 149 aas.		*UP of Ancylostoma ceylanicum* (nematoda)**

8.A.172.1.4	Uncharacterized protein of 310 aas.		UP of Taenia asiatica

8.A.172.1.5	Heat shock protein beta-9 of 160 aa		HSPβ9 of Molossus molossus

Examples:
TC#	Name	Organismal Type	Example
8.A.172.2.1	Hsp20/alpha crystallin family protein of 147 aas		*α-crystallin protein of Rhodanobacter* sp. C06**

8.A.172.2.2	Hsp20/alpha crystallin family protein of 169 aa		*HSP20 chaparone of Corynebacterium* sp.**

8.A.172.2.3	Hsp20/alpha crystallin family protein of 134 aa		Hsp20 of Chloroflexi bacterium

8.A.172.2.4	Hsp20/alpha crystallin family protein of 149 aa		Hsp20 of Nanoarchaeota archaeon (marine sediment metagenome)

8.A.172.2.5	Hsp20/alpha crystallin family protein of 166 aas		Hsp20 chaparone of Planctomycetaceae bacterium (hydrothermal vent metagenome)

8.A.172.2.6	Hsp20/alpha crystallin family protein of 167 aa		*Hsp20 of Natronolimnobius* sp.**