| First Author | Tian Y | Year | 2015 |
| Journal | Mol Brain | Volume | 8 |
| Issue | 1 | Pages | 70 |
| PubMed ID | 26521016 | Mgi Jnum | J:263408 |
| Mgi Id | MGI:6189342 | Doi | 10.1186/s13041-015-0156-4 |
| Citation | Tian Y, et al. (2015) VPS35-deficiency results in an impaired AMPA receptor trafficking and decreased dendritic spine maturation. Mol Brain 8(1):70 |
| abstractText | BACKGROUND: Vacuolar protein sorting 35 (VPS35), a key component of retromer, plays an important role in endosome-to-Golgi retrieval of membrane proteins. Dysfunction of VPS35/retromer is a risk factor for neurodegenerative disorders, including AD (Alzheimer's disease) and PD (Parkinson's disease). However, exactly how VPS35-deficiency contributes to AD or PD pathogenesis remains poorly understood. RESULTS: We found that VPS35-deficiency impaired dendritic spine maturation and decreased glutamatergic transmission. AMPA receptors, GluA1 and GluA2, are significantly reduced in purified synaptosomal and PSD fractions from VPS35-deficient brain. The surface levels of AMPA receptors are also decreased in VPS35-deficient neurons. Additionally, VPS35 interacted with AMPA-type receptors, GluA1 and GluA2. Overexpression of GluA2, but not GluA1, could partially restore the spine maturation deficit in VPS35-deficient neurons. CONCLUSIONS: These results provide evidence for VPS35's function in promoting spine maturation, which is likely through increasing AMPA receptor targeting to the postsynaptic membrane. Perturbation of such a VPS35/retromer function may contribute to the impaired glutamatergic transmission and pathogenesis of neurodegenerative disorders, such as AD and PD. |
