RRC ID 51529
Author Vieira N, Bessa C, Rodrigues AJ, Marques P, Chan FY, de Carvalho AX, Correia-Neves M, Sousa N.
Title Sorting nexin 3 mutation impairs development and neuronal function in Caenorhabditis elegans.
Journal Cell Mol Life Sci
Abstract The sorting nexins family of proteins (SNXs) plays pleiotropic functions in protein trafficking and intracellular signaling and has been associated with several disorders, namely Alzheimer's disease and Down's syndrome. Despite the growing association of SNXs with neurodegeneration, not much is known about their function in the nervous system. The aim of this work was to use the nematode Caenorhabditis elegans that encodes in its genome eight SNXs orthologs, to dissect the role of distinct SNXs, particularly in the nervous system. By screening the C. elegans SNXs deletion mutants for morphological, developmental and behavioral alterations, we show here that snx-3 gene mutation leads to an array of developmental defects, such as delayed hatching, decreased brood size and life span and reduced body length. Additionally, ∆snx-3 worms present increased susceptibility to osmotic, thermo and oxidative stress and distinct behavioral deficits, namely, a chemotaxis defect which is independent of the described snx-3 role in Wnt secretion. ∆snx-3 animals also display abnormal GABAergic neuronal architecture and wiring and altered AIY interneuron structure. Pan-neuronal expression of C. elegans snx-3 cDNA in the ∆snx-3 mutant is able to rescue its locomotion defects, as well as its chemotaxis toward isoamyl alcohol. Altogether, the present work provides the first in vivo evidence of the SNX-3 role in the nervous system.
Volume 75(11)
Pages 2027-2044
Published 2018-6-1
DOI 10.1007/s00018-017-2719-2
PII 10.1007/s00018-017-2719-2
PMID 29196797
PMC PMC11105199
MeSH Animals Body Size Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development* Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics* Gene Deletion* Gene Expression Regulation, Developmental Locomotion Longevity Nervous System / growth & development Nervous System / metabolism Nervous System Physiological Phenomena Neurons / metabolism Neurons / pathology Osmotic Pressure Oxidative Stress Phylogeny Sorting Nexins / genetics*
IF 6.496
Times Cited 0
C.elegans tm1595 tm2404 tm2423 tm3779 tm3790 tm5356 tm847