Rhodopsin plays a developmental role in photoreceptor morphogenesis within the Drosophila retina
Abstract
Mutations within the Drosophila rhodopsin gene, ninaE, result in retinal degeneration which is characterized by the complete dissolution of the rhabdomere, a highly ordered stack of microvilli within which rhodopsin molecules are arranged. Mutant photoreceptors are replete with membranous proliferations that have been determined to be rhabdomere membrane involuting into the cell body. These membranes which appear as thin ribbons of membrane in the electron microscope are parts of a continuous undulating sheet when summed in three dimensions. These membrane sheets are decorated with protein complexes containing F-actin and the unconventional myosin, two components of normal rhabdomeres. Key to the prevention of retinal degeneration in normal Drosophila is the correct formation of a catacomb-like structure at the rhabdomere base. This structure is absent in ninaE null mutants. An examination of rhabdomere morphogenesis in normal and mutant photoreceptors revealed that the rhabdomere base evolves late in development and is the first visible defect in the rhodopsin null mutant. The onset of rhodopsin transcription is under strict temporal regulation. Rhodopsin expression precedes and is required for the formation of the rhabdomere base. Null mutants that lack the rhabdomere base degenerate differently than hypomorphic mutants which produce the correct amounts of rhodopsin that is required to elaborate the catacomb-like architecture. Degeneration in hypomorphic mutants is a slow gradual process in which rhabdomeres disappear over time, deep intrusions of membrane are not present. The presence of the rhabdomere base in hypomorphic rhodopsin mutants prevents the catastrophic demise of the rhabdomere. A critical window during photoreceptor development exists in which rhodopsin is absolutely required. Infusion of rhodopsin during this narrow window is sufficient to maintain normal rhabdomere structure and physiology. However, the introduction of rhodopsin at times subsequent to this window is unable to suppress retinal degeneration. Photoreceptors that have been rescued by the addition of rhodopsin maintain their rhabdomeres well after rhodopsin levels have been depleted. It appears that the structural role of rhodopsin is transient in nature while its role in phototransduction is more perdurable. This work provides the groundwork for future studies aimed at further understanding the rhodopsin molecule.
Degree
Ph.D.
Advisors
Ready, Purdue University.
Subject Area
Neurology|Cellular biology|Molecular biology
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