Neural Maintenance Roles for the Matrix Receptor Dystroglycan and the Nuclear Anchorage Complex in Caenorhabditis elegans

• Published in: Genetics (Austin) Vol. 190; no. 4; pp. 1365 - 1377
• Main Authors: Johnson, Robert P, Kramer, James M
• Format: Journal Article
• Language: English
• Published: United States Genetics Society of America 01.04.2012
• Subjects: Animals; Caenorhabditis elegans - embryology; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell Nucleus - genetics; Cell Nucleus - metabolism; Chromosomes - genetics; Chromosomes - metabolism; Cytoplasm - genetics; Cytoplasm - metabolism; Developmental stages; Dystroglycans - genetics; Dystroglycans - metabolism; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - metabolism; Epistasis, Genetic; Gene Expression Regulation, Developmental; Genes, Helminth; Genetics; Investigations; Larva - genetics; Larva - growth & development; Larva - metabolism; Larvae; Larval development; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Muscle Contraction; Muscles - cytology; Muscles - embryology; Muscles - metabolism; Neurobiology; Neurons; Neurons - metabolism; Paralysis - genetics; Paralysis - pathology; Phenotype; Promoter Regions, Genetic; Protein Structure, Tertiary; Sequence Deletion; Stress, Physiological; Transgenes; Worms
• ISSN: 1943-2631; 0016-6731; 1943-2631
• DOI: 10.1534/genetics.111.136184

Recent studies in Caenorhabditis elegans have revealed specific neural maintenance mechanisms that protect soma and neurites against mispositioning due to displacement stresses, such as muscle contraction. We report that C. elegans dystroglycan (DG) DGN-1 functions to maintain the position of lumbar neurons during late embryonic and larval development. In the absence of DGN-1 the cell bodies of multiple lumbar neuron classes are frequently displaced anterior of their normal positions. Early but not later embryonic panneural expression of DGN-1 rescues positional maintenance, suggesting that dystroglycan is required for establishment of a critical maintenance pathway that persists throughout later developmental stages. Lumbar neural maintenance requires only a membrane-tethered N-terminal domain of DGN-1 and may involve a novel extracellular partner for dystroglycan. A genetic screen for similar lumbar maintenance mutants revealed a role for the nesprin/SYNE family protein ANC-1 as well as for the extracellular protein DIG-1, previously implicated in lumbar neuron maintenance. The involvement of ANC-1 reveals a previously unknown role for nucleus–cytoskeleton interactions in neural maintenance. Genetic analysis indicates that lumbar neuron position is maintained in late embryos by parallel DGN-1/DIG-1 and ANC-1–dependent pathways, and in larvae by separate DGN-1 and ANC-1 pathways. The effect of muscle paralysis on late embryonic- or larval-stage maintenance defects in mutants indicates that lumbar neurons are subject to both muscle contraction-dependent and contraction-independent displacement stresses, and that different maintenance pathways may protect against specific types of displacement stress.