Extracellular Proteins Needed for C. elegans Mechanosensation

Du, Hongping; Gu, Guoqiang; William, Chris M; Chalfie, Martin

doi:10.1016/s0896-6273(00)80035-5

Cited by 119 publications

(118 citation statements)

References 87 publications

Supporting

Mentioning

117

Contrasting

Unclassified

Order By: Relevance

“…3 B and D). Mutations in genes that encode the touch mechanosensory channel components MEC-2, MEC-4, MEC-6, and MEC-10 (10, 16-18), the extracellular matrix (ECM) protein MEC-9 (19), and the α-tubulin MEC-12 (10) led to type 1 pathology ( Fig. 3 A, B, and D).…”

Section: Resultsmentioning

confidence: 99%

Genetic analysis of age-dependent defects of the Caenorhabditis elegans touch receptor neurons

Pan

Peng

Chen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

156

239

View full text Add to dashboard Cite

Although many genes have been implicated in the pathogenesis of common neurodegenerative diseases, the genetic and cellular mechanisms that maintain neuronal integrity during normal aging remain elusive. Here we show that Caenorhabditis elegans touch receptor and cholinergic neurons display age-dependent morphological defects, including cytoskeletal disorganization, axon beading, and defasciculation. Progression of neuronal aging is regulated by DAF-2 and DAF-16 signaling, which also modulate adult life span. Mutations that disrupt touch-evoked sensory activity or reduce membrane excitability trigger accelerated neuronal aging, indicating that electrical activity is critical for adult neuronal integrity. Disrupting touch neuron attachment to the epithelial cells induces distinct neurodegenerative phenotypes. These results provide a detailed description of the age-dependent morphological defects that occur in identified neurons of C. elegans, demonstrate that the age of onset of these defects is regulated by specific genes, and offer experimental evidence for the importance of normal levels of neural activity in delaying neuronal aging. In the nematode Caenorhabditis elegans, age-dependent morphological changes are widespread in somatic tissues (2-4). However, there is little evidence for neuronal aging in C. elegans (3). The observations by Herndon et al. (3) suggest that neuronal loss or axon guidance defects do not occur in the aging C. elegans nervous system. It was also shown that whereas nuclear membranes of other somatic cell nuclei undergo drastic age-dependent deterioration, those of neuronal nuclei remain relatively intact in aging animals (4).There is, however, a clear age-dependent behavioral decline in C. elegans, including decrease in pharyngeal pumping, locomotion and chemotaxis (5). Evidence suggests that failure in neuronal activity could play a direct role in age-dependent behavioral deterioration. Cai and Sesti (6) showed that age-dependent oxidation of the C. elegans potassium channel KVS-1 causes sensory loss and that protection of neuronal KVS-1 from oxidation rescues agedependent decline in chemotaxis behavior. Electrical activity has been shown to be important for neuronal development (7) and was recently implicated in the survival or maintenance of adult mammalian and Drosophila neurons (8, 9). However, it is unclear how electrical activity promotes the integrity of adult neurons.In this paper, we address whether more subtle, subcellular changes occur in the aging C. elegans nervous system. Our results indicate that C. elegans neurons do develop age-dependent changes. Moreover, we show that electrical activity and normal attachment to the neighboring epithelial cells are required for the maintenance of adult touch receptor neurons.

show abstract

Section: Resultsmentioning

confidence: 99%

Genetic analysis of age-dependent defects of the Caenorhabditis elegans touch receptor neurons

Pan

Peng

Chen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

156

239

View full text Add to dashboard Cite

show abstract

“…Three such genes are mec-1, mec-5, and mec-9. mec-1 and mec-9 encode proteins with EGFand Kunitz-like domains that are expressed and secreted by the touch neurons [23,25], while mec-5 encodes a novel collagen generated by surrounding cells [23]. Both MEC-1 and MEC-5 proteins colocalize with the MEC-4 puncta along the touch neuron process, suggesting that they are concentrated around the mechanoreceptor channel complex [25].…”

Section: Proteins Required For Mechanosensationmentioning

confidence: 99%

Touch sensitivity in Caenorhabditis elegans

Bounoutas

Chalfie

2007

Pflugers Arch - Eur J Physiol

Self Cite

View full text Add to dashboard Cite

The nematode Caenorhabditis elegans was the first organism for which touch insensitive mutants were obtained. The study of the genes defective in these mutants has led to the identification of components of a mechanosensory complex needed for specific cells to sense gentle touch to the body. Multiple approaches using genetics, cell biology, biochemistry, and electrophysiology have characterized a channel complex, containing two DEG/ENaC pore-forming subunits and several other proteins, that transduces the touch response. Other mechanical responses, sensed by other cells using a variety of other components, are less well understood in C. elegans. Many of these other senses may use TRP channels, although DEG/ENaC channels have also been implicated.

show abstract

“…Secreted proteins have been shown to play important roles in mechanotransduction. For example, MEC-1 and MEC-9 are secreted by C. elegans touch neurons and genetically interact with the collagen MEC-5 (18,19). These three proteins are essential components of the C. elegans touch neuron mechanosensory complex (20).…”

mentioning

confidence: 99%

Genome-wide RNAi screening identifies protein damage as a regulator of osmoprotective gene expression

Lamitina

Huang²,

Strange³

2006

Proc. Natl. Acad. Sci. U.S.A.

163

257

View full text Add to dashboard Cite

The detection, stabilization, and repair of stress-induced damage are essential requirements for cellular life. All cells respond to osmotic stress-induced water loss with increased expression of genes that mediate accumulation of organic osmolytes, solutes that function as chemical chaperones and restore osmotic homeostasis. The signals and signaling mechanisms that regulate osmoprotective gene expression in animal cells are poorly understood. Here, we show that gpdh-1 and gpdh-2, genes that mediate the accumulation of the organic osmolyte glycerol, are essential for survival of the nematode Caenorhabditis elegans during osmotic stress. Expression of GFP driven by the gpdh-1 promoter (P gpdh-1::GFP) is detected only during hypertonic stress but is not induced by other stressors. Using Pgpdh-1::GFP expression as a phenotype, we screened Ϸ16,000 genes by RNAi feeding and identified 122 that cause constitutive activation of gpdh-1 expression and glycerol accumulation. Many of these genes function to regulate protein translation and cotranslational protein folding and to target and degrade denatured proteins, suggesting that the accumulation of misfolded proteins functions as a signal to activate osmoprotective gene expression and organic osmolyte accumulation in animal cells. Consistent with this hypothesis, 73% of these protein-homeostasis genes have been shown to slow age-dependent protein aggregation in C. elegans. Because diverse environmental stressors and numerous disease states result in protein misfolding, mechanisms must exist that discriminate between osmotically induced and other forms of stress-induced protein damage. Our findings provide a foundation for understanding how these damage-selectivity mechanisms function.Caenorhabditis elegans ͉ functional genomics ͉ organic osmolytes ͉ osmotic stress

show abstract

Extracellular Proteins Needed for C. elegans Mechanosensation

Cited by 119 publications

References 87 publications

Genetic analysis of age-dependent defects of the Caenorhabditis elegans touch receptor neurons

Genetic analysis of age-dependent defects of the Caenorhabditis elegans touch receptor neurons

Touch sensitivity in Caenorhabditis elegans

Genome-wide RNAi screening identifies protein damage as a regulator of osmoprotective gene expression

Contact Info

Product

Resources

About