Interaction with transducin depletes metarhodopsin III: a regulated retinal storage in visual signal transduction?
In the phototransduction pathway of rhodopsin, the metarhodopsin (Meta) III retinal storage form arises from the active G-protein binding Meta II by a slow spontaneous reaction through the Meta I precursor or by light absorption and photoisomerization, respectively. Meta III is a side product of the Meta II decay path and holds its retinal in the original binding site, with the Schiff base bond to the apoprotein reprotonated as in the dark ground state. It thus keeps the retinal away from the regeneration pathway in which the photolyzed all-trans-retinal is released. This study was motivated by our recent observation that Meta III remains stable for hours in membranes devoid of regulatory proteins, whereas it decays much more rapidly in situ. We have now explored the possibility of regulated formation and decay of Meta III, using intrinsic opsin tryptophan fluorescence and UV-visible and Fourier transform infrared spectroscopy. We find that a rapid return of Meta III into the regeneration pathway is triggered by the G-protein transducin (G(t)). Depletion of the retinal storage is initiated by a novel direct bimolecular interaction of G(t) with Meta III, which was previously considered inactive. G(t) thereby induces the transition of Meta III into Meta II, so that the retinylidene bond to the apoprotein can be hydrolyzed, and the retinal can participate again in the normal retinoid cycle. Beyond the potential significance for retinoid metabolism, this may provide the first example of a G-protein-catalyzed conversion of a receptor.
Institut für Medizinische Physik und Biophysik, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Schumannstrasse 20-21, D-10098 Berlin, Germany.
Kerstin
K
Zimmermann
Eglof
E
Ritter
Franz J
FJ
Bartl
Klaus Peter
KP
Hofmann
Martin
M
Heck
D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008027:Light; D010455:Peptides / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D012243:Rhodopsin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D015293:Transducin / Q000378:metabolism*
D010455:Peptides; D006153:Guanosine Diphosphate; C013110:metarhodopsins; D012243:Rhodopsin; D015293:Transducin