{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMelanosome transport and organelle biogenesis in pigment cells are orchestrated by an intricate network of motor proteins and accessory regulators. Early studies established that mutations in the motor complex—including MYO5A—lead to perinuclear clustering of melanosomes and diluted pigmentation, a defect that can be rescued by mutations in the dilute suppressor gene. In this context, melanoregulin (MREG) emerges as a key regulatory protein that not only modulates intercellular melanosome transfer through a shedding mechanism at melanocyte dendrites but also directs microtubule-dependent retrograde transport via an association with the dynein–dynactin complex. MREG further participates in endolysosomal maturation by coordinating LC3-associated phagocytosis and facilitating lysosomal degradation, including the regulation of proteolytic enzymes such as cathepsin-D. Additional studies have revealed that MREG interacts with other organelle-specific proteins—such as peripherin-2—to influence photoreceptor outer segment disk formation and regulate melanosome size by interfacing with components of the Hermansky–Pudlak syndrome BLOC pathway and intracellular G-protein–coupled receptors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast to these well‐characterized roles in pigmentation, recent work has begun to illuminate the function of myosin light chain 5 (MYL5) in a distinct physiological context. MYL5, a regulatory component of the myosin motor complex, appears to play a vital role in large‐scale cellular physiology and is now being investigated for its potential influence on clinical prognosis and immune cell infiltration in breast cancer. This emerging evidence points to MYL5 as a novel factor in modulating tumor biology, warranting further exploration into its mechanistic contributions and its potential as a prognostic marker or therapeutic target in breast cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "T Norene O'Sullivan, Xufeng S Wu, Rivka A Rachel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "dsu functions in a MYO5A-independent pathway to suppress the coat color of dilute mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0407339101"}], "href": "https://doi.org/10.1073/pnas.0407339101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15550542"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15550542"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kathleen Boesze-Battaglia, Hongman Song, Maxim Sokolov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The tetraspanin protein peripherin-2 forms a complex with melanoregulin, a putative membrane fusion regulator."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi061466i"}], "href": "https://doi.org/10.1021/bi061466i"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17260955"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17260955"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Monika Damek-Poprawa, Tanja Diemer, Vanda S Lopes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Melanoregulin (MREG) modulates lysosome function in pigment epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M808857200"}], "href": "https://doi.org/10.1074/jbc.M808857200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19240024"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19240024"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Norihiko Ohbayashi, Yuto Maruta, Morié Ishida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Melanoregulin regulates retrograde melanosome transport through interaction with the RILP-p150Glued complex in melanocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.094185"}], "href": "https://doi.org/10.1242/jcs.094185"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22275436"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22275436"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xufeng S Wu, Andreas Masedunskas, Roberto Weigert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Melanoregulin regulates a shedding mechanism that drives melanosome transfer from melanocytes to keratinocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1209397109"}], "href": "https://doi.org/10.1073/pnas.1209397109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22753477"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22753477"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xufeng S Wu, Jose A Martina, John A Hammer "}, {"type": "b", "children": [{"type": "t", "text": "Melanoregulin is stably targeted to the melanosome membrane by palmitoylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2012.08.064"}], "href": "https://doi.org/10.1016/j.bbrc.2012.08.064"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22940130"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22940130"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Rivka A Rachel, Kunio Nagashima, T Norene O'Sullivan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Melanoregulin, product of the dsu locus, links the BLOC-pathway and OA1 in organelle biogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0042446"}], "href": "https://doi.org/10.1371/journal.pone.0042446"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22984402"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22984402"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Laura S Frost, Vanda S Lopes, Frank P Stefano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of melanoregulin (MREG) enhances cathepsin-D secretion by the retinal pigment epithelium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Vis Neurosci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1017/S0952523813000096"}], "href": "https://doi.org/10.1017/S0952523813000096"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23611523"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23611523"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Laura S Frost, Vanda S Lopes, Alvina Bragin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Contribution of Melanoregulin to Microtubule-Associated Protein 1 Light Chain 3 (LC3) Associated Phagocytosis in Retinal Pigment Epithelium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Neurobiol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12035-014-8920-5"}], "href": "https://doi.org/10.1007/s12035-014-8920-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25301234"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25301234"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ashok K Rout, Xufeng Wu, Mary R Starich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Structure of Melanoregulin Reveals a Role for Cholesterol Recognition in the Protein's Ability to Promote Dynein Function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Structure (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.str.2018.07.009"}], "href": "https://doi.org/10.1016/j.str.2018.07.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30174147"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30174147"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Minghe Lv "}, {"type": "b", "children": [{"type": "t", "text": "MYL5 as a Novel Prognostic Marker is Associated with Immune Infiltrating in Breast Cancer: A Preliminary Study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast J (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2023/9508632"}], "href": "https://doi.org/10.1155/2023/9508632"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36846347"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36846347"}]}]}]}