title: VPS35-deficiency results in an impaired AMPA receptor trafficking and decreased dendritic spine maturation.
abstract: 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.
authors.affiliation: Department of Geriatrics and Department of Neurology, Xiangya Hospital, Central South University, ChangSha, 410008, China.|Department of Neuroscience & Regenerative Medicine and Department of Neurology, Medical College of Georgia, Augusta, GA, 30912, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Neuroscience & Regenerative Medicine and Department of Neurology, Medical College of Georgia, Augusta, GA, 30912, USA.|Charlie Norwood VA Medical Center, Augusta, GA, 30912, USA.
authors.forename: Fu-Lei
authors.initials: FL
authors.lastname: Tang
authors.affiliation: Department of Neuroscience & Regenerative Medicine and Department of Neurology, Medical College of Georgia, Augusta, GA, 30912, USA.
authors.forename: XiangDong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Neuroscience & Regenerative Medicine and Department of Neurology, Medical College of Georgia, Augusta, GA, 30912, USA.|Department of Traditional Chinese Medicine, Xia-Men University, Xia-Men, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wen
authors.affiliation: Department of Neuroscience & Regenerative Medicine and Department of Neurology, Medical College of Georgia, Augusta, GA, 30912, USA.|Charlie Norwood VA Medical Center, Augusta, GA, 30912, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
authors.affiliation: Department of Geriatrics and Department of Neurology, Xiangya Hospital, Central South University, ChangSha, 410008, China. bstang7398@163.com.
authors.forename: Bei-Sha
authors.initials: BS
authors.lastname: Tang
authors.affiliation: Department of Neuroscience & Regenerative Medicine and Department of Neurology, Medical College of Georgia, Augusta, GA, 30912, USA. wxiong@gru.edu.|Charlie Norwood VA Medical Center, Augusta, GA, 30912, USA. wxiong@gru.edu.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Xiong
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism; D021381:Protein Transport; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission; D033921:Vesicular Transport Proteins / Q000172:deficiency* / Q000378:metabolism
chemical_list: D005971:Glutamates; D018091:Receptors, AMPA; D033921:Vesicular Transport Proteins; C101274:Vps35 protein, mouse; D049452:Green Fluorescent Proteins