Author
Regulation of Endocannabinoid Signaling
Jun. 4, 2018—Calcium signaling drives many biochemical processes in dendritic spines, including synthesis of the major brain endocannabinoid, 2-arachidonylglycerol (2-AG), by diacylglycerol lipase-alpha (DGLa). We found that DGLa is another CaMKAP, and that CaMKII phosphorylates DGLa to inhibit 2-AG synthesis. Thus, in addition to activating DGLa, calcium recruits CaMKII to restrain synaptic 2-AG signaling, limiting the resulting...
Regulation of Calcium Channels
Jun. 4, 2018—Calcium entry via voltage-gated calcium channels drives numerous neuronal responses, including gene transcription and endocannabinoid synthesis. CaMKII is a key mediator of these downstream signals, but CaMKII also serves as a feedback regulator of several different types of calcium channel, generally facilitating calcium entry. We found that CaMKII directly interacts with and phosphorylates multiple types...
CaMKAPs
Jun. 4, 2018—We are testing the over-arching hypothesis that the activity, localization and ultimately biological function of CaMKII are modulated by interactions with a diverse array of CaMKII-associated proteins (CaMKAPs). Our lab was the first to show that the targeting of CaMKII to neuronal postsynaptic densities is dynamically regulated by the activation and autophosphorylation of CaMKII, and...
CaMKII Regulation
Jun. 4, 2018—The four mammalian CaMKII genes (alpha, beta, gamma, delta) encode more than 30 distinct CaMKII subunits due to extensive mRNA splicing. The N-terminal catalytic and regulatory domains are highly conserved across the subunit variants. CaMKII subunits assemble into dodecameric holoenzymes consisting of a stacked pair of hexameric rings due to homo- or hetero-meric interactions of...