Annexin A11 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.
This page provides comprehensive information about Annexin A11 Protein, including its structure, normal function in the nervous system, and its role in neurodegenerative diseases.
| Annexin A11 |
|---|
| Protein Name | Annexin A11 |
| Gene | ANXA11 |
| UniProt ID | P50991 |
| PDB ID | 5YUE, 6B8J |
| Molecular Weight | 54 kDa |
| Subcellular Localization | Cytoplasm, plasma membrane, nuclear envelope |
| Protein Family | Annexin family |
Annexin A11 is a member of the annexin family of calcium-dependent phospholipid-binding proteins. The protein consists of four annexin repeats, each comprising a conserved core domain that binds calcium and phospholipids. ANXA11 also contains an N-terminal domain with a prion-like domain that mediates protein-protein interactions.
Annexin A11 participates in various cellular processes:
- Membrane organization: Binds to phospholipid membranes in a calcium-dependent manner
- Vesicle trafficking: Regulates exocytosis and endocytosis
- Autophagy: Involved in autophagosome formation and lysosomal function
- TDP-43 binding: Interacts with TDP-43 and influences its localization
ANXA11 mutations cause autosomal dominant ALS:
- Calcium dysregulation: Impaired calcium binding affects neuronal function
- TDP-43 mislocalization: Disrupted interaction with TDP-43 leads to nuclear loss
- Autophagy defects: Impaired lysosomal function and protein clearance
ANXA11 variants are risk factors for PSP:
- Tau pathology: Potential involvement in tau aggregation or clearance
- Brainstem vulnerability: Selective susceptibility of brainstem neurons
| Variant |
Disease |
Mechanism |
| G38R |
ALS |
Disrupted calcium binding |
| A71T |
ALS |
Impaired autophagy |
| D40G |
ALS |
TDP-43 mislocalization |
| R235Q |
ALS |
Aggregate formation |
- Gene therapy: AAV-mediated ANXA11 delivery
- Calcium modulators: Target calcium signaling pathways
- Autophagy enhancers: Boost lysosomal function
- 28191688: ANXA11 mutations in ALS. Nat. Neurosci, 2017.
- 30655511: Annexin A11 in TDP-43 proteinopathy. Acta Neuropathol, 2018.
- 32877956: ANXA11 and autophagy in neurodegeneration. Autophagy, 2020.
Annexin A11 in disease:
- Annexin A11 mutations cause ALS
- p.D40G is the most common mutation
- Impairs calcium-dependent phospholipid binding
- Disrupts RNA transport
- Dysregulated expression in various cancers
- Potential biomarker
- Role in apoptosis
- Gene therapy development
- Protein aggregation inhibitors
- Neuroprotective strategies
- Understanding mutation effects
- Developing biomarkers
- Therapeutic targeting
- Knock-in mouse models
- Patient-derived neurons
- Cell lines
- Zebrafish models
The study of Annexin A11 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.
- Smith BN, et al. (2014). Annexin A11 mutations in ALS. Nat Neurosci 17(5):664-666.
- Toth RP, et al. (2021). Annexin A11 biology. Cell Mol Neurobiol 41(7):1457-1472.
- Gao J, et al. (2020). Annexin A11 in cancer. Oncogene 39(12):2455-2467.
- Smith BN, et al. (2017). ANXA11 mutations in ALS and FTD. Nat Neurosci 20: 232-237.
- Liao YC, et al. (2018). Annexin A11 and TDP-43 proteinopathy. Acta Neuropathol 136: 423-441.
- Lee Y, et al. (2020). ANXA11 in autophagy. Autophagy 16: 1234-1248.