VPS35-deficiency results in an impaired AMPA receptor trafficking and decreased dendritic spine maturation

Yun Tian, Fulei Tang, Xiang Dong Sun, Lei Wen, Lin Mei, Bei Sha Tang, Wencheng Xiong

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish (US)
Article number70
JournalMolecular brain
Volume8
Issue number1
DOIs
StatePublished - Oct 31 2015

Fingerprint

Dendritic Spines
AMPA Receptors
Protein Transport
Parkinson Disease
Alzheimer Disease
Neurodegenerative Diseases
Spine
Neurons
Endosomes
Membrane Proteins
Membranes

Keywords

  • AMPA receptor
  • Dendritic spine
  • Glutamatergic transmission
  • Retromer
  • VPS35

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

VPS35-deficiency results in an impaired AMPA receptor trafficking and decreased dendritic spine maturation. / Tian, Yun; Tang, Fulei; Sun, Xiang Dong; Wen, Lei; Mei, Lin; Tang, Bei Sha; Xiong, Wencheng.

In: Molecular brain, Vol. 8, No. 1, 70, 31.10.2015.

Research output: Contribution to journalArticle

Tian, Yun ; Tang, Fulei ; Sun, Xiang Dong ; Wen, Lei ; Mei, Lin ; Tang, Bei Sha ; Xiong, Wencheng. / VPS35-deficiency results in an impaired AMPA receptor trafficking and decreased dendritic spine maturation. In: Molecular brain. 2015 ; Vol. 8, No. 1.
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