TY - JOUR T1 - Transducin β-Subunit Can Interact with Multiple G Protein γ-Subunits to Enable Light Detection by Rod Photoreceptors JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0144-18.2018 SP - ENEURO.0144-18.2018 AU - Paige M. Dexter AU - Ekaterina S. Lobanova AU - Stella Finkelstein AU - William J. Spencer AU - Nikolai P. Skiba AU - Vadim Y. Arshavsky Y1 - 2018/05/17 UR - http://www.eneuro.org/content/early/2018/05/17/ENEURO.0144-18.2018.abstract N2 - The heterotrimeric G protein transducin mediates visual signaling in vertebrate photoreceptor cells. Many aspects of transducin’s function were learned from knockout mice lacking its individual subunits. Of particular interest is the knockout of its rod-specific γ-subunit (Gγ1). Two studies using independently generated mice documented that this knockout results in a considerable >60-fold reduction in light-sensitivity of affected rods, but provided different interpretations of how the remaining α-subunit (Gαt) mediates phototransduction without its cognate Gβ1γ1-subunit partner. One study found that the light-sensitivity reduction matched a corresponding reduction in Gαt content in the light-sensing rod outer segments and proposed that Gαt activation is supported by remaining Gβ1 associating with other Gγ subunit(s) naturally expressed in photoreceptors. In contrast, the second study reported the same light-sensitivity loss but a much lesser, only ∼6-fold reduction of Gαt and proposed that light responses of these rods do not require Gβγ at all. To resolve this controversy and elucidate the mechanism driving visual signaling in Gγ1 knockout rods, we analyzed both mouse lines side-by-side. We first determined that outer segments of both mice have identical Gαt content, which is reduced ∼65-fold from the wild type level. We further demonstrated that the remaining Gβ1 is present in a complex with endogenous Gγ2 and Gγ3 subunits and that these complexes exist in wild type rods as well. Together, these results argue against the idea that Gαt alone supports light responses of Gγ1 knockout rods and suggest that Gβ1γ1 is not unique in its ability to mediate vertebrate phototransduction.Significance Statement Phototransduction has been a valuable system for understanding the basic principles of G protein signaling. One question that has remained unanswered is whether the G protein α-subunit can support signaling without its cognate βγ partner complex. Previous studies investigating this question in photoreceptors of Gγ1 knockout mice came to mutually exclusive conclusions. We now resolve this controversy by showing that phototransduction in this knockout is supported by alternative βγ complexes rather than α-subunit alone. Most importantly, this study highlights functional interchangeability of different γ-subunits in the context of an intact in vivo system. ER -