SNX16 Regulates the Recycling of E-Cadherin through a Unique Mechanism of Coordinated Membrane and Cargo Binding

Structure. 2017 Aug 1;25(8):1251-1263.e5. doi: 10.1016/j.str.2017.06.015. Epub 2017 Jul 14.

Abstract

E-Cadherin is a major component of adherens junctions on cell surfaces. SNX16 is a unique member of sorting nexins that contains a coiled-coil (CC) domain downstream of the PX domain. We report here that SNX16 regulates the recycling trafficking of E-cadherin. We solved the crystal structure of PX-CC unit of SNX16 and revealed a unique shear shaped homodimer. We identified a novel PI3P binding pocket in SNX16 that consists of both the PX and the CC domains. Surprisingly, we showed that the PPII/α2 loop, which is generally regarded as a membrane insertion loop in PX family proteins, is involved in the E-cadherin binding with SNX16. We then proposed a multivalent membrane binding model for SNX16. Our study postulates a new mechanism for coordinated membrane binding and cargo binding for SNX family proteins in general, and provide novel insights into recycling trafficking of E-cadherin.

Keywords: E-cadherin; PX domain; SNX16; coiled-coil domain; epithelial-mesenchymal transition; mesenchymal-epithelial transition; recycling endosome; recycling trafficking; sorting nexin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cadherins / metabolism*
  • Cell Membrane / metabolism*
  • HEK293 Cells
  • Humans
  • MCF-7 Cells
  • Phosphatidylinositol Phosphates / chemistry
  • Phosphatidylinositol Phosphates / metabolism
  • Protein Binding
  • Protein Transport
  • Sorting Nexins / chemistry*
  • Sorting Nexins / metabolism

Substances

  • Cadherins
  • Phosphatidylinositol Phosphates
  • SNX16 protein, human
  • Sorting Nexins