Metarhodopsin eliciting PDA inactivated by Arrestin2

Figure 9. Inactivation of rhodopsin, and generation of the prolonged depolarizing afterpotential (PDA). Irradiation of fly (Drosophila, Calliphora) Rhl containing photoreceptor cells with blue light establishes a photoequilibrium containing about 70% metarhodopsin (M) and 30% rhodopsin (P). Due to the limited amount of Arrestin 2 (Arr2), only 30% of the total M can be inactivated (M') by binding of Arr2 (yellow field); 70% M remains in the active conformation (M*) and gives rise to a sustained electrical response of the receptor cell (PDA) through activation of the visual G-protein (Gq), followed by activation of phospholipase C(3 (PLCP) (blue field). Both, M* and M', are reconverted into (inactive) P by irradiation with red light. Following photoreconversion of M into P, Arr2 can only be released from the visual pigment if it is in the phosphorylated state (Arr2-P). Phosphorylation of Arr2 is a light-dependent reaction catalysed by Ca2+/calmodulin-dependent kinase (CaM Kinase). The sequence of Arr2 binding and Arr2 phosphorylation, as indicated here, is hypothetical. The Arr2 phosphatase has not been identified.

invertebrate species other than flies (Loligo pelagi [Mayeenuddin, unpublished], Limulus polyphemus [188], Ascalaphus macaronius [189]), arrestin-mediated metarhodopsin inactivation seems to be a general mechanism for turning off activated metarhodopsin in invertebrate photoreceptors.

A deactivation mechanism of phototransduction is also required for the active Gqa-subunit, at the next stage of the cascade. Generally the inactive, GDP bound state of G-proteins is restored by the intrinsic GTPase activity of Gqa. Experiments directed to investigate Gqa interaction with INAD linked PLC (Figure 8) indicated that Gqa does not reach this state unless it has interacted with PLC. This suggested that INAD-linked PLC has the function of a GTPase activating protein (GAP) [163], as has been previously shown for other phospholipase C types [190,191], Analyses of the response termination in inaD and norpA mutants of Drosophila not only revealed that INAD-linked PLC has the dual role of an effector enzyme of the phototransduction cascade and of a negative regulator of G-protein activity, they also demonstrated that the occupance of a sufficient number of binding sites on the INAD signalling complex is a prerequisite for the high temporal and intensity resolution of visual responses [192],

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