Energy storage and release at times of food excess or fasting are carefully coordinated processes that depend on the appropriate differentiation of mesenchymal stem cells into mature adipocytes (adipogenesis) forming white adipose tissue (WAT) and on regulatory signals for storage (lipogenesis) or mobilization (lipolysis) of triacylglycerides (TAGs) from lipid droplets. It is widely recognized that cAMP signaling via protein kinase A (PKA) is important both in adipogenesis and for hormonal control and lipolysis in WAT. A kinase anchoring proteins (AKAPs) target PKA to distinct subcellular compartments in close proximity to its specific substrates thereby providing spatial and temporal specificity in the mediation of biological effects controlled by the cAMP-PKA pathway. This review will provide an updated overview of some of the sites of regulation by cAMP in adipogenesis and lipolysis and the involvement of AKAPs and highlighting, as a recent example, the AKAP Optical Atrophy 1 (OPA1) and its role in the phosphorylation of Perilipin to induce lipolysis.

OPA1 haploinsufficiency impairs formation of DLX1/2-positive GABAergic neurons Reduced OPA1 levels significantly alter the transcriptional circuitry in neural cells Expression of the pioneer factor FOXG1 is decreased in OPA1+/À neural progenitor cells Impaired FOXG1 expression correlates with increased CpG methylation at its promoter

Reformation of the nuclear envelope at the end of mitosis involves the recruitment of the B-type lamin phosphatase PP1 to nuclear membranes by A-kinase anchoring protein AKAP149. PP1 remains associated to AKAP149 throughout G1 but dissociates from AKAP149 when AKAP149 is phosphorylated at the G1/S transition. We examine here the role of phosphorylation of serines flanking the RVXF PP1-binding motif of AKAP149, on PP1 anchoring. The use of AKAP149 peptides encompassing the RVXF motif and five flanking serines, either wild type (wt) or bearing S-->A or S-->D mutations, specifically shows that phosphorylation of S151 or S159 abolishes PP1 binding to immobilized AKAP149. Peptides with S151 or S159 as the only wt serine residue trigger dissociation of PP1 from immunoprecipitated AKAP149, whereas S151/159D mutants are ineffective. Furthermore, immunoprecipitated AKAP149 from purified G1-phase nuclear envelopes binds PKA and PKC in overlay assays. PKA binding to AKAP149 in vitro is unaffected by the presence of PKC or PP1, and similarly, PKC binding is independent of PKA or PP1. The immunoprecipitated AKAP149 complex contains PKA and PKC activities. Both AKAP149-associated PKA and PKC serine-phosphorylate immunoprecipitated AKAP149 in vitro; however, only PKC-mediated phosphorylation promotes dissociation of PP1 from the AKAP. The results suggest a putative temporally and spatially controlled mechanism promoting release of PP1 from AKAP149. AKAP149 emerges as a scaffolding protein for multiple protein kinases and phosphatases that may be involved in the integration of intracellular signals that converge at the nuclear envelope.