Distant insulin signaling regulates vertebrate pigmentation through the sheddase bace2 Journal Article
| Authors: | Zhang, Y. M.; Zimmer, M. A.; Guardia, T.; Callahan, S. J.; Mondal, C.; Di Martino, J.; Takagi, T.; Fennell, M.; Garippa, R.; Campbell, N. R.; Bravo-Cordero, J. J.; White, R. M. |
| Article Title: | Distant insulin signaling regulates vertebrate pigmentation through the sheddase bace2 |
| Abstract: | Patterning of vertebrate melanophores is essential for mate selection and protection from UV-induced damage. Patterning can be influenced by circulating long-range factors, such as hormones, but it is unclear how their activity is controlled in recipient cells to prevent excesses in cell number and migration. The zebrafish wanderlust mutant harbors a mutation in the sheddase bace2 and exhibits hyperdendritic and hyperproliferative melanophores that localize to aberrant sites. We performed a chemical screen to identify suppressors of the wanderlust phenotype and found that inhibition of insulin/PI3Kγ/mTOR signaling rescues the defect. In normal physiology, Bace2 cleaves the insulin receptor, whereas its loss results in hyperactive insulin/PI3K/mTOR signaling. Insulin B, an isoform enriched in the head, drives the melanophore defect. These results suggest that insulin signaling is negatively regulated by melanophore-specific expression of a sheddase, highlighting how long-distance factors can be regulated in a cell-type-specific manner. Zhang et al. demonstrate that insulin signaling affects pigment patterning in zebrafish. They show that the local response to insulin signaling is regulated by Bace2, a melanocyte-enriched sheddase that cleaves the insulin receptor. © 2018 |
| Keywords: | melanocyte; insulin; pi3k; zebrafish; mtor; insulin receptor; bace2; melanophore; pigment patterning |
| Journal Title: | Developmental Cell |
| Volume: | 45 |
| Issue: | 5 |
| ISSN: | 1534-5807 |
| Publisher: | Cell Press |
| Date Published: | 2018-06-04 |
| Start Page: | 580 |
| End Page: | 594.e7 |
| Language: | English |
| DOI: | 10.1016/j.devcel.2018.04.025 |
| PROVIDER: | scopus |
| PMCID: | PMC5991976 |
| PUBMED: | 29804876 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 July 2018 -- Source: Scopus |
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