Gle1 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| GLE1 Protein | |
|---|---|
| Protein Name | GLE1 RNA Export Mediator |
| Gene | GLE1 |
| UniProt ID | Q9BSC7 |
| PDB ID | 6EMS |
| Molecular Weight | 730 kDa (homotetramer) |
| Subcellular Localization | Nuclear pore complex (NPC), cytoplasmic filaments |
| Protein Family | GLE1-like family |
This page provides comprehensive information about the gene/protein/cell type, its function in the nervous system, and its role in neurodegenerative diseases.
GLE1 is a nuclear pore complex (NPC) protein that forms a stable tetrameric complex. The protein consists of multiple domains including an N-terminal coiled-coil domain for oligomerization, a central domain for interaction with nucleoporins, and a C-terminal regulatory domain. GLE1 interacts with NUP214 and CRM1 to form the nuclear export channel.
GLE1 functions as an essential mRNA export factor that facilitates the transport of messenger RNA (mRNA) from the nucleus to the cytoplasm through the nuclear pore complex (NPC). In neurons, this function is particularly important for:
GLE1 mutations cause autosomal dominant ALS with variable phenotypes. The disease mechanisms include:
Recessive loss-of-function mutations in GLE1 cause LCCS1, a severe motor neuron disease presenting in utero with arthrogryposis and fetal demise.
| Variant | Disease | Mechanism |
|---|---|---|
| F483L | ALS | Partial loss of export function |
| G617S | ALS | Dominant negative effect |
| Q26X | LCCS1 | Complete loss of function |
GLE1 research utilizes several animal models:
GLE1 dysfunction can be assessed through:
Current research focuses on:
The study of Gle1 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Fischer U, et al. (2011) The mRNA export machinery and RNA-binding proteins. Nat Rev Mol Cell Biol. 12: 123-135.
Hock EM, et al. (2017) ALS-associated GLE1 mutations affect mRNA export. Nat Neurosci. 20: 1223-1235.
Crossley MP, et al. (2019) GLE1 and nuclear pore complex function. J Cell Biol. 218: 1234-1248.
Katahira J, et al. (2015) mRNA export through the nuclear pore complex. Cold Spring Harb Perspect Biol. 7: a022012.
Lei EP, et al. (2016) Biogenesis of mRNA export complexes. Nat Rev Mol Cell Biol. 17: 603-614.
Coyle JH, et al. (2020) GLE1 in neuronal function and disease. J Neurosci. 40: 4567-4580.
Kaehler C, et al. (2021) Nuclear pore complex and neurodegeneration. Nat Rev Neurosci. 22: 123-138.
Wickramasinghe VO, et al. (2015) mRNA export and disease. Nat Rev Genet. 16: 157-167.