RRC ID 59578
Author Richardson CE, Yee C, Shen K.
Title A hormone receptor pathway cell-autonomously delays neuron morphological aging by suppressing endocytosis.
Journal PLoS Biol
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.
Volume 17(10)
Pages e3000452
Published 2019-10-1
DOI 10.1371/journal.pbio.3000452
PMID 31589601
PMC PMC6797217
MeSH 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
IF 8.386
Times Cited 0
C.elegans tm5159 tm1556 tm1447