Cacng2 Protein Stargazin Calcium Channel Gamma 2 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
CACNG2 (Calcium Channel Gamma-2 Subunit), also known as stargazin, is a gamma subunit of voltage-gated calcium channels. Beyond its role in calcium channels, stargazin is renowned for its critical function in AMPA receptor trafficking, making it essential for synaptic plasticity and excitatory neurotransmission.
| Property |
Value |
| Protein Name |
Voltage-gated calcium channel gamma-2 subunit (Stargazin) |
| Gene Symbol |
CACNG2 |
| UniProt ID |
Q9Y698 |
| Molecular Weight |
~41 kDa |
| Protein Length |
366 amino acids |
| Chromosomal Location |
22q12.3 |
The CACNG2/stargazin protein has a unique structure:
- Four Transmembrane Domains: Similar to other gamma subunits
- N-terminal Extracellular Domain: Involved in protein interactions
- C-terminal PDZ-binding Motif: Critical for binding to PSD-95 and related proteins
- Modulates high-voltage-activated calcium channel function
- Affects channel trafficking and gating properties
- Critical for synaptic targeting of AMPA receptors
- Anchors AMPA receptors at the postsynaptic density
- Interacts with PSD-95 family proteins via PDZ domains
- Essential for long-term potentiation (LTP)
- Required for long-term depression (LTD)
- Regulates dendritic spine morphology
- Stargazin dysfunction in AD models
- Impaired AMPA receptor trafficking
- Contributes to synaptic plasticity deficits
- CACNG2 mutations cause severe epileptic encephalopathy
- The stargazer mouse model has spontaneous seizures
- Disrupted glutamatergic signaling
- Strong genetic association with ASD
- Synaptic dysfunction through AMPA receptor mislocalization
- Found in multiple autism gene studies
- Genetic variants increase risk
- Altered glutamatergic neurotransmission
| Strategy |
Agent |
Status |
| Ampakines |
CX516, CX1739 |
Clinical trials |
| PSD-95 Modulators |
- |
Research |
| Gene Therapy |
AAV-stargazin |
Experimental |
- Stargazer Mice: Natural mutant with ataxia and seizures
- CACNG2 Knockout Mice: Impaired AMPA receptor trafficking
- Transgenic Overexpression: Enhanced LTP
The study of Cacng2 Protein Stargazin Calcium Channel Gamma 2 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.
- Chen L, et al. (2000). Stargazin regulates synaptic targeting of AMPA receptors. Neuron. 28(3):873-886.
- Tomita S, et al. (2003). Stargazin controls AMPA receptor pharmacology. Nature. 423(6939):649-652.
- Letts VA, et al. (1998). The mouse stargazer gene encodes a neuronal Ca2+ channel gamma subunit. Nat Genet. 19(4):340-347.
- Bats C, et al. (2007). The coupling of AMPA receptor trafficking to synaptic plasticity. Phil Trans R Soc B. 362(1480):745-752.