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The reorientation of the Golgi apparatus is crucial for cell migration and is regulated by multi-polarity signals. A number of non-centrosomal microtubules anchor at the surface of the Golgi apparatus and play a vital role in the Golgi reorientation, but how the Golgi are regulated by polarity signals remains unclear. Calmodulin-regulated spectrin-associated protein 2 (CAMSAP2) is a protein that anchors microtubules to the Golgi, a cellular organelle. Our research indicates that CAMSAP2 is dynamically localized at the Golgi during its reorientation processing. Further research shows that CAMSAP2 is potentially regulated by a polarity signaling molecule called MARK2, which interacts with CAMSAP2. We used mass spectrometry to find that MARK2 phosphorylates CAMSAP2 at serine 835, which affects its interaction with the Golgi associated protein USO1 but not with CG-NAP or CLASPs. This interaction is critical for anchoring microtubules to the Golgi during cell migration, altering microtubule polarity distribution, and aiding Golgi reorientation. Our study reveals an important signaling pathway in Golgi reorientation during cell migration, which can provide insights for research in cancer cell migration, immune response, and targeted drug development.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
* 1.Removal of Unsupported Claims:To ensure scientific rigor, we removed all claims and data related to MARK2 localization at the Golgi apparatus due to insufficient supporting evidence. This adjustment refines the focus of our manuscript and eliminates unsupported conclusions. 2.New Experiments and Data Improvements:Dynamic Imaging of Golgi Dynamics: We conducted live-cell imaging experiments to directly observe the Golgi apparatus during cell migration. These data confirm that the Golgi undergoes a transient dispersed state before reorganization, as shown in Supplementary Figure 2A. Rescue Experiments: We overexpressed GFP-MARK2 in MARK2 KO cells, which successfully restored Golgi architecture and CAMSAP2 Golgi localization, validated MARK2 role in CAMSAP2 regulation (Supplementary Figures 3 C-E). Enhanced Quantification: Quantitative analyses were updated and standardized. For instance, Pearsons coefficient was consistently used to analyze CAMSAP2 localization on the Golgi (e.g., Figures 1B-E, 3A-C, and 6F-G), while Golgi state in wound-edge cells was uniformly evaluated based on Golgi-nucleus positioning (Figures 2D-E, 5A-B). 3.Data Presentation and Clarity: Signal intensities in key figures were enhanced for better visualization (e.g., Figures 1A, 5A, 6G). Figure captions were revised for consistency, and the number of independent experiments was clearly indicated throughout the manuscript.