title: Integrin-linked kinase modulates longevity and thermotolerance in C. elegans through neuronal control of HSF-1.
abstract: Integrin-signaling complexes play important roles in cytoskeletal organization and cell adhesion in many species. Components of the integrin-signaling complex have been linked to aging in both Caenorhabditis elegans and Drosophila melanogaster, but the mechanism underlying this function is unknown. Here, we investigated the role of integrin-linked kinase (ILK), a key component of the integrin-signaling complex, in lifespan determination. We report that genetic reduction of ILK in both C. elegans and Drosophila increased resistance to heat stress, and led to lifespan extension in C. elegans without majorly affecting cytoskeletal integrity. In C. elegans, longevity and thermotolerance induced by ILK depletion was mediated by heat-shock factor-1 (HSF-1), a major transcriptional regulator of the heat-shock response (HSR). Reduction in ILK levels increased hsf-1 transcription and activation, and led to enhanced expression of a subset of genes with roles in the HSR. Moreover, induction of HSR-related genes, longevity and thermotolerance caused by ILK reduction required the thermosensory neurons AFD and interneurons AIY, which are known to play a critical role in the canonical HSR. Notably, ILK was expressed in neighboring neurons, but not in AFD or AIY, implying that ILK reduction initiates cell nonautonomous signaling through thermosensory neurons to elicit a noncanonical HSR. Our results thus identify HSF-1 as a novel effector of the organismal response to reduced ILK levels and show that ILK inhibition regulates HSF-1 in a cell nonautonomous fashion to enhance stress resistance and lifespan in C. elegans.
authors: Development, Aging and Regeneration Program, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
authors: Caroline
authors: C
authors: Kumsta
authors: Tsui-Ting
authors: TT
authors: Ching
authors: Mayuko
authors: M
authors: Nishimura
authors: Andrew E
authors: AE
authors: Davis
authors: Sara
authors: S
authors: Gelino
authors: Hannah H
authors: HH
authors: Catan
authors: Xiaokun
authors: X
authors: Yu
authors: Chu-Chiao
authors: CC
authors: Chu
authors: Binnan
authors: B
authors: Ong
authors: Siler H
authors: SH
authors: Panowski
authors: Nathan
authors: N
authors: Baird
authors: Rolf
authors: R
authors: Bodmer
authors: Ao-Lin
authors: AL
authors: Hsu
authors: Malene
authors: M
authors: Hansen
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D018869:Heat-Shock Response / Q000235:genetics / Q000502:physiology*; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D000099200:Scaffold Protein ILK
chemical_list: D029742:Caenorhabditis elegans Proteins; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; D000099200:Scaffold Protein ILK; C474710:heat shock factor-1, C elegans
keywords: C. elegans; HSF-1; PAT-4/ILK; aging; heat-shock response; integrin signaling