Details

Autor(en) / Beteiligte

• Cheng, Louise Y.
• Bailey, Andrew P.
• Leevers, Sally J.
• Ragan, Timothy J.
• Driscoll, Paul C.
• Gould, Alex P.

Titel

Anaplastic Lymphoma Kinase Spares Organ Growth during Nutrient Restriction in Drosophila

Ist Teil von

• Cell, 2011-08, Vol.146 (3), p.435-447

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2011

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Developing animals survive periods of starvation by protecting the growth of critical organs at the expense of other tissues. Here, we use Drosophila to explore the as yet unknown mechanisms regulating this privileged tissue growth. As in mammals, we observe in Drosophila that the CNS is more highly spared than other tissues during nutrient restriction (NR). We demonstrate that anaplastic lymphoma kinase (Alk) efficiently protects neural progenitor (neuroblast) growth against reductions in amino acids and insulin-like peptides during NR via two mechanisms. First, Alk suppresses the growth requirement for amino acid sensing via Slimfast/Rheb/TOR complex 1. And second, Alk, rather than insulin-like receptor, primarily activates PI3-kinase. Alk maintains PI3-kinase signaling during NR as its ligand, Jelly belly (Jeb), is constitutively expressed from a glial cell niche surrounding neuroblasts. Together, these findings identify a brain-sparing mechanism that shares some regulatory features with the starvation-resistant growth programs of mammalian tumors. [Display omitted] ► Drosophila neuroblasts, unlike other cells, grow during nutrient restriction (NR) ► Growth requires anaplastic lymphoma kinase (Alk) and its ligand Jelly belly ► Alk supresses InR and TOR but constitutively activates PI3K and TORC1 targets ► Ectopic Alk signaling in a nonspared tissue protects its growth during NR