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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MSK Authors
  1. Toshimitsu Takagi
    6 Takagi
  2. Richard Mark White
    27 White
  3. Ralph James Garippa
    14 Garippa
  4. Myles Ashley Fennell
    18 Fennell
  5. Milena Annika Zimmer
    2 Zimmer
  6. Yan Zhang
    3 Zhang