α-COP binding to the survival motor neuron protein SMN is required for neuronal process outgrowth

Hongxia Li, Sara K. Custer, Timra Gilson, Le Thi Hao, Christine E. Beattie, Elliot Androphy

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Spinal muscular atrophy (SMA), a heritable neurodegenerative disease, results from insufficient levels of the survival motor neuron (SMN) protein. α-COP binds to SMN, linking the COPI vesicular transport pathway to SMA. Reduced levels of α-COP restricted development of neuronal processes in NSC-34 cells and primary cortical neurons. Remarkably, heterologous expression of human α-COP restored normal neurite length and morphology in SMN-depleted NSC-34 cells in vitro and zebrafish motor neurons in vivo. We identified single amino acid mutants of α-COP that selectively abrogate SMN binding, retain COPImediated Golgi-ER trafficking functionality, but were unable to support neurite outgrowth in cellular and zebrafish models of SMA. Taken together, these demonstrate the functional role of COPI association with theSMNprotein in neuronal development.

Original languageEnglish (US)
Pages (from-to)7295-7307
Number of pages13
JournalHuman Molecular Genetics
Volume24
Issue number25
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

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