Sgt1p is a highly conserved eucaryotic protein that is required for both SCF (Skp1p/Cdc53p-Cullin-F-box)-mediated ubiquitination and kinetochore function in yeast. We show here that Sgt1p is also involved in the cyclic AMP (cAMP) pathway in Saccharomyces cerevisiae. SGT1 is an allele-specific suppressor of cdc35-1, a thermosensitive mutation in the leucine-rich repeat domain of the adenylyl cyclase Cyr1p/Cdc35p. We demonstrate that Sgt1p and Cyr1p/Cdc35p physically interact and that the activity of the cAMP pathway is affected in an sgt1 conditional mutant. Sequence analysis suggests that Sgt1p has features of a cochaperone. Thus, Sgt1p is a novel activator of adenylyl cyclase in S. cerevisiae and may function in the assembly or the conformational activation of specific multiprotein complexes.

Although electromagnetic brain stimulation is a promising treatment in neurology and psychiatry, clinical outcomes are variable, and underlying mechanisms are ill-defined, which impedes the development of new effective stimulation protocols. Here, we show, in vivo and ex vivo, that repetitive transcranial magnetic stimulation at low-intensity (LI-rTMS) induces axon outgrowth and synaptogenesis to repair a neural circuit. This repair depends on stimulation pattern, with complex biomimetic patterns being particularly effective, and the presence of cryptochrome, a putative magnetoreceptor. Only repair-promoting LI-rTMS patterns up-regulated genes involved in neuronal repair; almost 40% of were cryptochrome targets. Our data open a new framework to understand the mechanisms underlying structural neuroplasticity induced by electromagnetic stimulation. Rather than neuronal activation by induced electric currents, we propose that weak magnetic fields act through cryptochrome to activate cellular signaling cascades. This information opens new routes to optimize electromagnetic stimulation and develop effective treatments for different neurological diseases.