Identification of pericentriolar matrix protein 1 (PCM1) as a novel scaffold for Protein Kinase A (PKA) and NIMA-related kinase 10 (NEK10)

The pericentriolar material 1 (PCM1) assembles a molecular platform around the pericentriolar matrix and centrosome that is essential for cell division and microtubule dynamics, and plays a critical role in different aspects of mitosis and ciliogenesis. Here, we report an additonal layer of complexity and found that PCM1 nucleates a signaling complex at the pericentriolar matrix, which includes PKA and NEK10. By co-clustering two distinct signaling enzymes, PCM1 controls critical aspects of mammalian ciliogenesis. Within the PCM1 complex, PKA regulates NEK10 localization and stability, efficiently coupling cAMP signaling to the ubiquitin-proteasome system (UPS). In this context, PCM1 acts as relay that senses, transmits and integrates cAMP and mitogenic signals generated at cell membrane, regulating biological events at the pericentriolar matrix area and primary cilium. The molecular characterization of relevant protein complexes at specific sub-cellular compartments and understanding the role of scaffold platform in critical aspects of cell biology will likely contribute to the design of novel therapeutic approaches for human diseases.