Function and regulation of photoreceptor phosphodiesterase (PDE6) in the visual signaling pathway.
Abstract
Abstract
This chapter focuses on the catalytic and regulatory features of the photoreceptor phosphodiesterase 6 (PDE6) that make it suitable as the central effector of the visual transduction pathway. Photoreceptor PDE6 is one of the 11 PDE family members that comprise the class I cyclic nucleotide PDE superfamily. These enzymes regulate the cellular levels of cAMP and/or cGMP. Some PDE families are specific for one cyclic nucleotide, while others are dual substrate enzymes. All class I PDEs possess a conserved catalytic region of approximately 270 amino acids located toward the C-terminus of the primary sequence. Most PDE families contain a regulatory region located within their N-terminal region. The primary sequences of the catalytic subunits of rod PDE6 are coded by two distinct genes, β (gene name, PDE6A) and β (gene name, PDE6B), which form a catalytic heterodimer, β α. A PDE6 catalytic subunit consists of highly conserved regulatory GAF domains, a catalytic domain, and a C-terminus that is posttranslationally modified. There are no X-ray crystal structures available for PDE6 holoenzyme or for individual catalytic or regulatory domains of the protein. The catalytic domain of PDE6 is likely to consist of 16 α-helices arranged into three subdomains. Two metal ions such as zinc and magnesium are coordinated by a group of 6 invariant residues present in all 11 class I PDE families, and form an integral part of the active site of PDE6. The ability of light-activated PDE6 to hydrolyze cGMP at the diffusion-controlled limit is essential for light-induced changes in cGMP levels to occur on the millisecond timescale needed for the physiological response of rods and cones to illumination.
Department
Molecular, Cellular and Biomedical Sciences
Publication Date
2010
Publisher
Elsevier
Digital Object Identifier (DOI)
10.1016/B978-0-12-374145-5.00177-7
Document Type
Book Chapter
Recommended Citation
Cote, R.H., Cahill, K.B. "Function and regulation of photoreceptor phosphodiesterase (PDE6) in the visual signaling pathway." Handbook of Cell Signaling. Ralph A. Bradshaw and Edward A. Davis, (Eds.) New York: Academic Press, 2010. pp. 1445-1451.
Rights
© 2010 Elsevier Inc. All rights reserved.