TECPR2 Cooperates with LC3C to Regulate COPII-Dependent ER Export

Mol Cell. 2015 Oct 1;60(1):89-104. doi: 10.1016/j.molcel.2015.09.010.

Abstract

Hereditary spastic paraplegias (HSPs) are a diverse group of neurodegenerative diseases that are characterized by axonopathy of the corticospinal motor neurons. A mutation in the gene encoding for Tectonin β-propeller containing protein 2 (TECPR2) causes HSP that is complicated by neurological symptoms. While TECPR2 is a human ATG8 binding protein and positive regulator of autophagy, the exact function of TECPR2 is unknown. Here, we show that TECPR2 associates with several trafficking components, among them the COPII coat protein SEC24D. TECPR2 is required for stabilization of SEC24D protein levels, maintenance of functional ER exit sites (ERES), and efficient ER export in a manner dependent on binding to lipidated LC3C. TECPR2-deficient HSP patient cells display alterations in SEC24D abundance and ER export efficiency. Additionally, TECPR2 and LC3C are required for autophagosome formation, possibly through maintaining functional ERES. Collectively, these results reveal that TECPR2 functions as molecular scaffold linking early secretion pathway and autophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Autophagy*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • HeLa Cells
  • Humans
  • Microtubule-Associated Proteins / metabolism*
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Transport*
  • Spastic Paraplegia, Hereditary / genetics*
  • Spastic Paraplegia, Hereditary / metabolism
  • Vesicular Transport Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • BLOC1S1 protein, human
  • Carrier Proteins
  • GABARAP protein, human
  • MAP1LC3C protein, human
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • SEC24D protein, human
  • TECPR2 protein, human
  • Vesicular Transport Proteins

Associated data

  • PDB/5DCN