Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023:1415:449-456.
doi: 10.1007/978-3-031-27681-1_66.

Perspectives on Retinal Dolichol Metabolism, and Visual Deficits in Dolichol Metabolism-Associated Inherited Disorders

Sriganesh Ramachandra Rao  1   2 , Steven J Pittler  3 , Steven J Fliesler  4   5
Affiliations
Review

Perspectives on Retinal Dolichol Metabolism, and Visual Deficits in Dolichol Metabolism-Associated Inherited Disorders

Sriganesh Ramachandra Rao et al. Adv Exp Med Biol. 2023.

Abstract

De novo synthesis of dolichol (Dol) and dolichyl phosphate (Dol-P) is essential for protein glycosylation. Herein, we provide a brief overview of Dol and Dol-P synthesis and the maintenance of their cellular content. Retinal Dol metabolism and the requirement of Dol-linked oligosaccharide synthesis in the neural retina also are discussed. There are recently discovered and an emerging class of rare congenital disorders that affect Dol metabolism, involving the genes DHDDS, NUS1, SRD5A3, and DOLK. Further understanding of these congenital disorders is evolving, based upon studies utilizing yeast and murine models, as well as clinical reports of these rare disorders. We summarize the known visual deficits associated with Dol metabolism disorders, and identify the need for generation and characterization of suitable animal models of these disorders to elucidate the underlying molecular and cellular mechanisms of the associated retinopathies.

Keywords: DHDDS; DOLK; DOLPP1; Dolichol; Dolichyl phosphate; NUS1; Protein glycosylation; Retinitis pigmentosa; SRD5A3; Vision defects.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

    1. Edani BH, Grabinska KA, Zhang R, Park EJ, Siciliano B, Surmacz L, et al. Structural elucidation of the cis-prenyltransferase NgBR/DHDDS complex reveals insights in regulation of protein glycosylation. Proc. Natl. Acad. Sci. U. S. A. 2020;117(34):20794–802. - PubMed - PMC
    1. Bar-El ML, Vankova P, Yeheskel A, Simhaev L, Engel H, Man P, et al. Structural basis of heterotetrameric assembly and disease mutations in the human cis-prenyltransferase complex. Nat. Commun. 2020;11(1):5273. - PubMed - PMC
    1. Ramachandra Rao S, Fliesler SJ. Cholesterol homeostasis in the vertebrate retina: biology and pathobiology. J. Lipid Res. 2021;62:100057. - PubMed - PMC
    1. Ramachandra Rao S, Skelton LA, Wu F, Onysk A, Spolnik G, Danikiewicz W, et al. Retinal degeneration caused by rod-specific dhdds ablation occurs without concomitant inhibition of protein N-glycosylation. iScience. 2020;23(6):101198. - PubMed - PMC
    1. Cantagrel V, Lefeber DJ, Ng BG, Guan Z, Silhavy JL, Bielas SL, et al. SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder. Cell. 2010;142(2):203–17. - PubMed - PMC

LinkOut - more resources