ArticleProceedings of the National Academy of Sciences of the United States of America2017
Myosin Va's adaptor protein melanophilin enforces track selection on the microtubule and actin networks in vitro.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Spatially-resolved subtype progression reveals metabolic vulnerabilities in pancreatic ductal adenocarcinoma.Molecular cancer · 2026Article
- Cellular phospho-signaling map of the enigmatic serine/threonine kinase MAST2.Biochemistry and biophysics reports · 2025Article
- Disrupting melanin transfer: innovative strategy for anti-pigmentation drug discovery.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Cross-tissue transcriptome-wide association studies identify genetic susceptibility genes for prostate cancer.BMC cancer · 2025Article
- Melanosome Transport and Processing in Skin Pigmentation: Mechanisms and Targets for Pigmentation Modulation.International journal of molecular sciences · 2025Review
- AID-2×RBD27, an auxin-inducible degron-based Rab27 trapper that reversibly inhibits the function of Rab27A in melanocytes.Journal of cell science · 2025Article
- Melanophilin-induced primary cilia promote pancreatic cancer metastasis.Cell death & disease · 2025Article
- Article
- Inflammatory response: The target for treating hyperpigmentation during the repair of a burn wound.Frontiers in immunology · 2023Review
- DYF-5/MAK-dependent phosphorylation promotes ciliary tubulin unloading.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- MITF in Normal Melanocytes, Cutaneous and Uveal Melanoma: A Delicate Balance.International journal of molecular sciences · 2022Review
- In vivo Roles of Rab27 and Its Effectors in Exocytosis.Cell structure and function · 2021Review
- New twists in actin-microtubule interactions.Molecular biology of the cell · 2021Review
- Roles and regulation of myosin V interaction with cargo.Advances in biological regulation · 2021Review
- Evolutionary selection of alleles in the melanophilin gene that impacts on prostate organ function and cancer risk.Evolution, medicine, and public health · 2021Article
- Whitening effect of novel peptide mixture by regulating melanosome biogenesis, transfer and degradation.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2021Article
- Actin and Myosin in Non-Neuronal Exocytosis.Cells · 2020Review
- Molecular underpinnings of cytoskeletal cross-talk.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Altered mitochondrial trafficking as a novel mechanism of cancer metastasis.Cancer reports (Hoboken, N.J.) · 2020Review
- Research Techniques Made Simple: Cell Biology Methods for the Analysis of Pigmentation.The Journal of investigative dermatology · 2020Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
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 phosphorylation of the ABD closely recapitulated the previously described in vivo phosphorylation pattern. Unexpectedly, we found that phosphorylation of the ABD affected neither the interaction of the complex with actin nor its movement along actin tracks. Surprisingly, the phosphorylation state of melanophilin was instead important for reversible association with microtubules in vitro. Dephosphorylated melanophilin preferred binding to microtubules even in the presence of actin, whereas phosphorylated melanophilin associated with actin. Indeed, when actin and microtubules were present simultaneously, melanophilin's phosphorylation state enforced track selection of the Rab27a/melanophilin/myosin Va transport complex. Collectively, our results unmasked the regulatory dominance of the melanophilin adaptor protein over its associated motor and offer an unexpected mechanism by which filaments of the cytoskeletal network compete for the moving organelles to accomplish directional transport on the cytoskeleton in vivo.
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