{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:19:15Z","timestamp":1785406755178,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32373106"],"award-info":[{"award-number":["32373106"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32373106"],"award-info":[{"award-number":["32373106"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Key Research and Development Program of China","award":["2022YFD1201600"],"award-info":[{"award-number":["2022YFD1201600"]}]},{"name":"Chongqing Fishery Technology Innovation Union","award":["CQFTIU202501-7"],"award-info":[{"award-number":["CQFTIU202501-7"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Adenylate cyclase 5 (Adcy5) generates cyclic adenosine monophosphate (cAMP) downstream of G protein-coupled receptor signaling, yet its role in vertebrate pigmentation remains incompletely understood. Here, we generated a CRISPR\/Cas9-mediated adcy5 knockout line in Nile tilapia (Oreochromis niloticus) to investigate its function in chromatophore biology. Loss of adcy5 resulted in a pronounced disruption of body coloration, characterized by the absence of vertical black bars and a global reduction in pigmentation. Despite this, chromatophore number was largely unaffected, indicating that Adcy5 is not required for pigment cell specification but is essential for functional pigmentation. At the cellular level, pigment granules in melanophores and erythrophores failed to undergo dispersion and instead remained constitutively aggregated, revealing a primary defect in intracellular pigment granule transport. Consistently, adcy5 mutants exhibited reduced expression of key melanogenesis-associated genes, including mitfa, tyrb, tyrp1a, and tyrp1b, accompanied by decreased melanin content across multiple tissues. Pharmacological activation of cAMP signaling partially rescued the pigment dispersion defect, whereas stimulation of upstream \u03b1-MSH signaling produced only limited effects, placing Adcy5 upstream of intracellular cAMP production within the pigment regulatory cascade. Importantly, we further demonstrate that Adcy5 is required for erythrophore pigment granule dispersion, extending its functional role beyond melanophore biology. Together, these findings identify Adcy5 as a conserved regulator integrating cAMP-dependent pigment synthesis and granule transport across multiple chromatophore types in teleost fish.<\/jats:p>","DOI":"10.3390\/cells15151347","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:08:14Z","timestamp":1785161294000},"page":"1347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adenylate Cyclase 5 (Adcy5) Deficiency Impairs Pigment Granule Dispersion in Melanophores and Erythrophores in Nile Tilapia"],"prefix":"10.3390","volume":"15","author":[{"given":"Jia","family":"Sun","sequence":"first","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, School of Life Sciences, Southwest University, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, School of Life Sciences, Southwest University, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawen","family":"Yao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, School of Life Sciences, Southwest University, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, School of Life Sciences, Southwest University, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, School of Life Sciences, Southwest University, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Ju","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, School of Life Sciences, Southwest University, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongsheng","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, School of Life Sciences, Southwest University, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0507-6525","authenticated-orcid":false,"given":"Xingyong","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, School of Life Sciences, Southwest University, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4967-524X","authenticated-orcid":false,"given":"Deshou","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, School of Life Sciences, Southwest University, Chongqing 400715, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.1021\/ja01570a086","article-title":"The Formation of a Cyclic Dianhydrodiadenylic Acid (I) by the Alkaline Degradation of Adenosine-5\u2019-Triphosphoric Acid (II)1","volume":"79","author":"Cook","year":"1957","journal-title":"J. Am. Chem. Soc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/S0021-9258(19)77422-5","article-title":"Formation of a Cyclic Adenine Ribonucleotide by Tissue Particles","volume":"232","author":"Rall","year":"1958","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1159\/000166277","article-title":"Physiological Roles for G Protein-Regulated Adenylyl Cyclase Isoforms: Insights from Knockout and Overexpression Studies","volume":"17","author":"Sadana","year":"2009","journal-title":"Neurosignals"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4477","DOI":"10.1111\/febs.70022","article-title":"A Signal Transduction Blind Spot: The Function of Adenylyl Cyclase Transmembrane Domains","volume":"292","author":"Dowsell","year":"2025","journal-title":"FEBS J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e21771","DOI":"10.7554\/eLife.21771","article-title":"Lipid Droplet Biology and Evolution Illuminated by the Characterization of a Novel Perilipin in Teleost Fish","volume":"6","author":"Granneman","year":"2017","journal-title":"eLife"},{"key":"ref_6","first-page":"245","article-title":"New Insights into Melanosome Transport in Vertebrate Pigment Cells","volume":"272","author":"Aspengren","year":"2009","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1111\/acel.12152","article-title":"Reduced Malignancy as a Mechanism for Longevity in Mice with Adenylyl Cyclase Type 5 Disruption","volume":"13","author":"Chen","year":"2014","journal-title":"Aging Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e97597","DOI":"10.15252\/embj.201797597","article-title":"STIM1 Activation of Adenylyl Cyclase 6 Connects Ca2+ and cAMP Signaling during Melanogenesis","volume":"37","author":"Motiani","year":"2018","journal-title":"EMBO J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/pcmr.12386","article-title":"Adenylate cyclase 5 is Required for Melanophore and Male Pattern Development in the Guppy (Poecilia reticulata)","volume":"28","author":"Kottler","year":"2015","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zhang, L., Wan, M., Tohti, R., Jin, D., and Zhong, T.P. (2022). Requirement of Zebrafish Adcy3a and Adcy5 in Melanosome Dispersion and Melanocyte Stripe Formation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214182"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/0092-8674(86)90821-4","article-title":"Bidirectional Pigment Granule Movements of Melanophores are Regulated by Protein Phosphorylation and Dephosphorylation","volume":"47","author":"Rozdzial","year":"1986","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1083\/jcb.142.3.803","article-title":"Regulation of Organelle Movement in Melanophores by Protein Kinase A (PKA), Protein Kinase C (PKC), and Protein Phosphatase 2A (PP2A)","volume":"142","author":"Reilein","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_13","first-page":"523","article-title":"Effects of Photoresponses on the Movement of Pigment Granule in Erythrophores of Xiphophorus helleri and the Mechanism","volume":"14","author":"Liu","year":"2007","journal-title":"J. Fish. Sci. China"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1242\/bio.20146742","article-title":"The Influence of Chromatic Background on the Photosensitivity of Tilapia Erythrophores","volume":"3","author":"Chen","year":"2014","journal-title":"Biol. Open"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"112861","DOI":"10.1016\/j.jphotobiol.2024.112861","article-title":"Nonvisual System-Mediated Body Color Change in Fish Reveals Nonvisual Function of Opsin 3 in Skin","volume":"252","author":"Zhang","year":"2024","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"dev202114","DOI":"10.1242\/dev.202114","article-title":"A Gene Regulatory Network Combining Pax3\/7, Sox10 and Mitf Generates Diverse Pigment Cell Types in Medaka and Zebrafish","volume":"150","author":"Miyadai","year":"2023","journal-title":"Development"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1038\/s41467-023-36876-4","article-title":"Zebrafish Pigment Cells Develop Directly from Persistent Highly Multipotent Progenitors","volume":"14","author":"Subkhankulova","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"739151","DOI":"10.1016\/j.aquaculture.2022.739151","article-title":"Knockout of Microphthalmia-Associated Transcription Factor (Mitf) Confers a Red and Yellow Tilapia with Few Pigmented Melanophores","volume":"565","author":"Wang","year":"2023","journal-title":"Aquaculture"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1093\/jhered\/esab018","article-title":"Nile Tilapia: A Model for Studying Teleost Color Patterns","volume":"112","author":"Wang","year":"2021","journal-title":"J. Hered."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e87","DOI":"10.1002\/imt2.87","article-title":"Using PhyloSuite for Molecular Phylogeny and Tree-Based Analyses","volume":"2","author":"Xiang","year":"2023","journal-title":"Imeta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"W78","DOI":"10.1093\/nar\/gkae268","article-title":"Interactive Tree of Life (iTOL) v6: Recent Updates to the Phylogenetic Tree Display and Annotation Tool","volume":"52","author":"Letunic","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_22","first-page":"100518","article-title":"Dual-Receptor Switch Bifurcates Kitlga for Nile Tilapia Pigmentation","volume":"5","author":"Yao","year":"2026","journal-title":"Water Biol. Secur."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1034\/j.1600-0749.2000.130203.x","article-title":"Cyclic AMP a Key Messenger in the Regulation of Skin Pigmentation","volume":"13","author":"Ballotti","year":"2000","journal-title":"Pigment. Cell Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/pcmr.12920","article-title":"Cyclic Adenosine Monophosphate (cAMP) Signaling in Melanocyte Pigmentation and Melanomagenesis","volume":"34","author":"Bang","year":"2021","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.abb.2014.07.003","article-title":"Cyclic AMP (cAMP) Signaling in Melanocytes and Melanoma","volume":"563","author":"Setaluri","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1016\/j.cub.2003.10.027","article-title":"Switching between Microtubule- and Actin-Based Transport Systems in Melanophores is Controlled by cAMP Levels","volume":"13","author":"Rodionov","year":"2003","journal-title":"Curr. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.jtbi.2006.07.024","article-title":"Modeling of Pattern Regulation in Melanophores","volume":"244","author":"Dinh","year":"2007","journal-title":"J. Theor. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1083\/jcb.96.2.354","article-title":"Analysis of the Role of Microtubules and Actin in Erythrophore Intracellular Motility","volume":"96","author":"Beckerle","year":"1983","journal-title":"J. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/S0092-8674(00)80947-2","article-title":"Developmental Regulation of Vesicle Transport in Drosophila Embryos: Forces and Kinetics","volume":"92","author":"Welte","year":"1998","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1083\/jcb.200105055","article-title":"Interactions and Regulation of Molecular Motors in Xenopus Melanophores","volume":"156","author":"Gross","year":"2002","journal-title":"J. Cell Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/15\/1347\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:15:20Z","timestamp":1785384920000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/15\/1347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":30,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cells15151347"],"URL":"https:\/\/doi.org\/10.3390\/cells15151347","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]}}}