Regulation of retinal membrane guanylyl cyclase (RetGC) by negative calcium feedback and RD3 protein

Pflugers Arch. 2021 Sep;473(9):1393-1410. doi: 10.1007/s00424-021-02523-4. Epub 2021 Feb 3.

Abstract

This article presents a brief overview of the main biochemical and cellular processes involved in regulation of cyclic GMP production in photoreceptors. The main focus is on how the fluctuations of free calcium concentrations in photoreceptors between light and dark regulate the activity of retinal membrane guanylyl cyclase (RetGC) via calcium sensor proteins. The emphasis of the review is on the structure of RetGC and guanylyl cyclase activating proteins (GCAPs) in relation to their functional role in photoreceptors and congenital diseases of photoreceptors. In addition to that, the structure and function of retinal degeneration-3 protein (RD3), which regulates RetGC in a calcium-independent manner, is discussed in detail in connections with its role in photoreceptor biology and inherited retinal blindness.

Keywords: GCAP; GUCY2D; Guanylyl cyclase (Guanylate cyclase); Photoreceptors; RD3; Retinal degeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling / physiology
  • Eye Proteins / chemistry
  • Eye Proteins / metabolism*
  • Feedback, Physiological / physiology*
  • Guanylate Cyclase / chemistry
  • Guanylate Cyclase / metabolism*
  • Humans
  • Photoreceptor Cells, Vertebrate / chemistry
  • Photoreceptor Cells, Vertebrate / metabolism*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Retina / chemistry
  • Retina / metabolism

Substances

  • Eye Proteins
  • RD3 protein, human
  • Guanylate Cyclase
  • Calcium