biostudies-literatureOberhofer AEuropean Research CouncilDeutsche ForschungsgemeinschaftMedical Research CouncilE4714-E4723https://www.ebi.ac.uk/biostudies/studies/S-EPMC5474823biostudies-literatureUnknown114(24)Pigment organelles, or melanosomes, are transported by kinesin, dynein, and myosin motors. As such, melanosome transport is an excellent model system to study the functional relationship between the microtubule- and actin-based transport systems. In mammalian melanocytes, it is well known that the Rab27a/melanophilin/myosin Va complex mediates actin-based transport in vivo. However, pathways that regulate the overall directionality of melanosomes on the actin/microtubule networks have not yet been delineated. Here, we investigated the role of PKA-dependent phosphorylation on the activity of the actin-based Rab27a/melanophilin/myosin Va transport complex in vitro. We found that melanophilin, specifically its C-terminal actin-binding domain (ABD), is a target of PKA. Notably, in vitro phosphProceedings of the National Academy of Sciences of the United States of AmericaMyosin Va's adaptor protein melanophilin enforces track selection on the microtubule and actin networks in vitro.PMC5474823G1100063335623SFB863Rosenfeld YOberhofer AStepp WLCleetus AMueller-Planitz FSpieler PHume ANOkten ZfalseMyosin Va's adaptor protein melanophilin enforces track selection on the microtubule and actin networks in vitro.Pigment organelles, or melanosomes, are transported by kinesin, dynein, and myosin motors. As such, melanosome transport is an excellent model system to study the functional relationship between the microtubule- and actin-based transport systems. In mammalian melanocytes, it is well known that the Rab27a/melanophilin/myosin Va complex mediates actin-based transport in vivo. However, pathways that regulate the overall directionality of melanosomes on the actin/microtubule networks have not yet been delineated. Here, we investigated the role of PKA-dependent phosphorylation on the activity of the actin-based Rab27a/melanophilin/myosin Va transport complex in vitro. We found that melanophilin, specifically its C-terminal actin-binding domain (ABD), is a target of PKA. Notably, in vitro phosph2017-01-01T00:00:00Z2017 Jun2025-04-25T19:19:10.258Z2019-03-27T02:47:55ZS-EPMC54748232855931910.1073/pnas.1619473114