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| ASPM (Abnormal Spindle-like Microcephaly-associated) |
|---|
| Gene | ASPM |
| UniProt | Q9P2E3 |
| PDB Structures | 4MTX, 4MTY |
| Molecular Weight | 347 kDa |
| Localization | Centrosome, spindle poles |
| Protein Family | ASPM family |
Aspm 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 this protein. See the content below for detailed information.
ASPM is the most frequently mutated gene in primary microcephaly. It encodes a centrosomal protein that regulates mitotic spindle function and is essential for normal neurogenesis during brain development.
ASPM is one of the largest proteins in the human genome:
- N-terminal calponin homology domains (x2) - microtubule binding
- Multiple CH domains - repeated throughout protein
- C-terminal ASPM domain - conserved microcephaly domain
- Spindle pole targeting domain - centrosomal localization
- Phosphorylation sites - cell cycle regulation
The protein contains 81 predicted calponin homology domains, making it structurally unique.
During neurogenesis, ASPM plays critical roles:
- Spindle orientation - maintains symmetric cell divisions
- Centrosome function - proper mitotic apparatus
- Neural progenitor proliferation - expands the progenitor pool
- Cleavage plane specification - determines division symmetry
- Cytokinesis - completes cell division
ASPM mutations cause the most common form of autosomal recessive primary microcephaly:
- Frequency - ~30-50% of MCPH cases
- Head circumference - >3-4 SD below mean
- Brain size - reduced cerebral cortex
- Cognitive outcome - usually mild intellectual disability
- Brain structure - simplified gyral pattern
- Spindle orientation defects - shifts from symmetric to asymmetric divisions
- Reduced progenitor pool - fewer neural stem cells
- Accelerated neurogenesis - premature differentiation
- Reduced neuron number - smaller brain
- Normal neuronal function - preserved cognitive capacity per neuron
- ASPM overexpression in gliomas
- Potential cancer stem cell marker
- Role in cell proliferation
- Bond J, et al. (2003). "ASPM is a major determinant of cerebral cortical size." Nat Genet. 35(4):298-301. DOI:10.1038/ng1259
- Fish JL, et al. (2008). "ASPM specifically maintains symmetric proliferative divisions of neuroepithelial cells." Development. 135(10):1793-1803. DOI:10.1242/dev.020255
- Kouprina N, et al. (2005). "Essential role of ASPM in centriole duplication." J Cell Biol. 168(7):973-982. DOI:10.1083/jcb.200411031
The study of Aspm 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.