The spinal muscular atrophy disease protein SMN is linked to the Golgi network

PLoS One. 2012;7(12):e51826. doi: 10.1371/journal.pone.0051826. Epub 2012 Dec 17.

Abstract

Proximal spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by deficiency of the ubiquitous Survival of Motor Neuron (SMN) protein. SMN has been shown to be transported in granules along the axon and moved through cytoskeletal elements. However, the role and nature of SMN granules are still not well characterized. Here, using immunocytochemical methods and time-lapse studies we show that SMN granules colocalize with the Golgi apparatus in motor neuron-like NSC34 cells. Electron microscopy clearly revealed that SMN granules are transported into the Golgi stack and aggregate in the trans-Golgi apparatus. SMN granules are characterized as either coated or un-coated and behave like regulated secretory granules. Treatment of cells with monensin to disrupt Golgi-mediated granule secretion decreased SMN expression in neurites and caused growth cone defects similar to those seen in SMN knockdown cells. Knockdown of Cop-α, the protein that coats vesicles transporting proteins between the Golgi compartments, caused SMN granule accumulation in the Golgi apparatus. In addition to the well-studied role of SMN in small nuclear ribonucleoprotein (SnRNP) assembly, this work links SMN granules with the Golgi network and thus sheds light on Golgi-mediated SMN granule transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Nucleus / metabolism
  • Coat Protein Complex I / metabolism
  • Cytoplasm / metabolism*
  • Cytoplasmic Granules / metabolism*
  • Fluorescent Antibody Technique
  • Golgi Apparatus / metabolism*
  • Immunoenzyme Techniques
  • Mice
  • Microscopy, Electron, Transmission
  • Motor Neurons / cytology
  • Motor Neurons / metabolism*
  • Muscular Atrophy, Spinal / metabolism*
  • Neurites / metabolism
  • Protein Transport
  • RNA, Small Interfering / genetics
  • Survival of Motor Neuron 1 Protein / antagonists & inhibitors
  • Survival of Motor Neuron 1 Protein / physiology*
  • Time-Lapse Imaging

Substances

  • Coat Protein Complex I
  • RNA, Small Interfering
  • Survival of Motor Neuron 1 Protein

Grant support

This work was supported by the research grant NSC100-2321-B-001-008 from the National Science Council, Taiwan (http://web1.nsc.gov.tw) and Academia Sinica (AS034006 and AS022323; http://www.sinica.edu.tw/index.shtml). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.