A hormone receptor pathway cell-autonomously delays neuron morphological aging by suppressing endocytosis

PLoS Biol. 2019 Oct 7;17(10):e3000452. doi: 10.1371/journal.pbio.3000452. eCollection 2019 Oct.

Abstract

Neurons have a lifespan that parallels that of the organism and are largely irreplaceable. Their unusually long lifespan predisposes neurons to neurodegenerative disease. We sought to identify physiological mechanisms that delay neuron aging in Caenorhabditis elegans by asking how neuron morphological aging is arrested in the long-lived, alternate organismal state, the dauer diapause. We find that a hormone signaling pathway, the abnormal DAuer Formation (DAF) 12 nuclear hormone receptor (NHR) pathway, functions cell-intrinsically in the dauer diapause to arrest neuron morphological aging, and that same pathway can be cell-autonomously manipulated during normal organismal aging to delay neuron morphological aging. This delayed aging is mediated by suppressing constitutive endocytosis, which alters the subcellular localization of the actin regulator T cell lymphoma Invasion And Metastasis 1 (TIAM-1), thereby decreasing age-dependent neurite growth. Intriguingly, we show that suppressed endocytosis appears to be a general feature of cells in diapause, suggestive that this may be a mechanism to halt the growth and other age-related programs supported by most endosome recycling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Cellular Senescence / genetics
  • Diapause / genetics*
  • Endocytosis / genetics
  • Endosomes / metabolism
  • Gene Expression Regulation, Developmental
  • Genotype
  • Longevity / genetics*
  • Neurons / cytology
  • Neurons / metabolism*
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Signal Transduction
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1 / genetics*
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1 / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • DAF-12 protein, C elegans
  • Receptors, Cytoplasmic and Nuclear
  • T-Lymphoma Invasion and Metastasis-inducing Protein 1
  • TIAM-1 protein, C elegans