Visual Signal Transduction (Heck Lab)
Dr. Heck’s research focuses on the following topics:
- the molecular mechanism and
- kinetics of visual signal transduction as well as the retinoid cycle.
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Workgroup Visual Signal Transduction
The workgroup of Dr. Heck concentrates on the following topics:
- the enzymatic and structural characterization of PDE6,
- the molecular basis of retinal uptake and release from opsin,
- the influence of receptor phosphorylation and arrestin binding on retinal uptake and release, and on rhodopsin photo-chemistry,
- the stoichiometry and conformational dynamics of arrestin-rhodopsin interactions.
Background
In the rod cells of the retina resides the photoreceptor rhodopsin, which consists of the 7-transmembrane helical protein opsin and a covalently-attached ligand 11-cis-retinal. Light-absorption leads to the isomerization of 11-cis-retinal to all-trans-retinal, which induces a series of activating conformational changes in the receptor protein. The initial light-signal is amplified by a reaction cascade: active rhodopsin activates many G proteins, which then activate cGMP-specific phosphodiesterase (PDE6). Ultimately the light-signal leads to a hyperpolarization of the rod cell membrane and altered neurotransmitter release at the synapse. Shortly after light-activation, rhodopsin is phosphorylated by rhodopsin kinase, which allows binding of the protein arrestin. Arrestin binding blocks further G protein activation. In contrast to many other retinal proteins found in nature, vertebrate rhodopsin cannot be regenerated by light. All-trans-retinal dissociates from the receptor protein following hydrolysis of the covalent bond between retinal and opsin. Subsequently, opsin is regenerated to rhodopsin by the uptake of 11-cis-retinal. A complex enzymatic machinery, called the retinoid cycle, exists to convert all-trans-retinal to 11-cis-retinal.
Biophysical methods
A wide array of biochemical and biophysical methods are used, for example:
- isolation of the constituent proteins from native tissues and protein purification from different expression systems,
- site-directed mutagenesis and labelling,
- fluorescence spectroscopy,
- UV-Vis spectroscopy, and
- kinetic modelling.