Vps35-deficiency impairs SLC4A11 trafficking and promotes corneal dystrophy

Wei Liu, Fulei Tang, Sen Lin, Kai Zhao, Lin Mei, Jian Ye, Wencheng Xiong

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Vps35 (vacuolar protein sorting 35) is a major component of retromer that selectively promotes endosome-to-Golgi retrieval of transmembrane proteins. Dysfunction of retromer is a risk factor for the pathogenesis of Parkinson’s disease (PD) and Alzheimer’s disease (AD). However, Vps35/retromer’s function in the eye or the contribution of Vps35-deficiency to eye degenerative disorders remains to be explored. Here we provide evidence for a critical role of Vps35 in mouse corneal dystrophy. Vps35 is expressed in mouse and human cornea. Mouse cornea from Vps35 heterozygotes (Vps35+/-) show features of dystrophy, such as loss of both endothelial and epithelial cell densities, disorganizations of endothelial, stroma, and epithelial cells, excrescences in the Descemet membrane, and corneal edema. Additionally, corneal epithelial cell proliferation was reduced in Vps35-deficient mice. Intriguingly, cell surface targeting of SLC4A11, a membrane transport protein (OH- /H+ /NH3 /H2O) of corneal endothelium, whose mutations have been identified in patients with corneal dystrophy, was impaired in Vps35-deficient cells and cornea. Taken together, these results suggest that SLC4A11 appears to be a Vps35/retromer cargo, and Vps35-regulation of SLC4A11 trafficking may underlie Vps35/retromer regulation of corneal dystrophy.

Original languageEnglish (US)
Article numbere0184906
JournalPLoS One
Volume12
Issue number9
DOIs
StatePublished - Sep 1 2017

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protein transport
Protein Transport
Sorting
Proteins
Cornea
cornea
Epithelial Cells
epithelial cells
mice
Endothelial Cells
Endothelial cells
Descemet Membrane
Corneal Edema
Corneal Endothelium
Membrane Transport Proteins
eyes
Endosomes
Heterozygote
endosomes
transmembrane proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Vps35-deficiency impairs SLC4A11 trafficking and promotes corneal dystrophy. / Liu, Wei; Tang, Fulei; Lin, Sen; Zhao, Kai; Mei, Lin; Ye, Jian; Xiong, Wencheng.

In: PLoS One, Vol. 12, No. 9, e0184906, 01.09.2017.

Research output: Contribution to journalArticle

Liu, Wei ; Tang, Fulei ; Lin, Sen ; Zhao, Kai ; Mei, Lin ; Ye, Jian ; Xiong, Wencheng. / Vps35-deficiency impairs SLC4A11 trafficking and promotes corneal dystrophy. In: PLoS One. 2017 ; Vol. 12, No. 9.
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