Multiprotein complexes of the survival of motor neuron protein SMN with Gemins traffic to neuronal processes and growth cones of motor neurons

Honglai Zhang, Lei Xing, Wilfried Rossoll, Hynek Wichterle, Robert H. Singer, Gary J. Bassell

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Spinal muscular atrophy (SMA), a progressive neurodegenerative disease affecting motor neurons, is caused by mutations or deletions of the SMN1 gene encoding the survival of motor neuron (SMN) protein. In immortalized non-neuronal cell lines, SMN has been shown to form a ribonucleoprotein (RNP) complex with Gemin proteins, which is essential for the assembly of small nuclear RNPs (snRNPs). An additional function of SMN in neurons has been hypothesized to facilitate assembly of localized messenger RNP complexes. We have shown that SMN is localized in granules that are actively transported into neuronal processes and growth cones. In cultured motor neurons, SMN granules colocalized with ribonucleoprotein Gemin proteins but not spliceosomal Sm proteins needed for snRNP assembly. Quantitative analysis of endogenous protein colocalization in growth cones after three-dimensional reconstructions revealed a statistically nonrandom association of SMN with Gemin2 (40%) and Gemin3 (48%). SMN and Gemin containing granules distributed to both axons and dendrites of differentiated motor neurons. A direct interaction between SMN and Gemin2 within single granules was indicated by fluorescence resonance energy transfer analysis of fluorescently tagged and overexpressed proteins. High-speed dual-channel imaging of live neurons depicted the rapid and bidirectional transport of the SMN-Gemin complex. The N terminus of SMN was required for the recruitment of Gemin2 into cytoplasmic granules and enhanced Gemin2 stability. These findings provide new insight into the molecular composition of distinct SMN multiprotein complexes in neurons and motivation to investigate deficiencies of localized RNPs in SMA.

Original languageEnglish (US)
Pages (from-to)8622-8632
Number of pages11
JournalJournal of Neuroscience
Volume26
Issue number33
DOIs
StatePublished - Aug 16 2006

Fingerprint

Multiprotein Complexes
Growth Cones
Motor Neurons
SMN Complex Proteins
Proteins
Small Nuclear Ribonucleoproteins
Spinal Muscular Atrophy
Ribonucleoproteins
Neurons
Cytoplasmic Granules
Fluorescence Resonance Energy Transfer
Sequence Deletion
Gene Deletion
Dendrites
Neurodegenerative Diseases
Axons
Cell Survival

Keywords

  • Growth cone
  • Motor neuron disease
  • mRNA localization
  • RNA granules
  • SMA
  • SMN
  • Spinal muscular atrophy
  • Survival of motor neuron protein

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Multiprotein complexes of the survival of motor neuron protein SMN with Gemins traffic to neuronal processes and growth cones of motor neurons. / Zhang, Honglai; Xing, Lei; Rossoll, Wilfried; Wichterle, Hynek; Singer, Robert H.; Bassell, Gary J.

In: Journal of Neuroscience, Vol. 26, No. 33, 16.08.2006, p. 8622-8632.

Research output: Contribution to journalArticle

Zhang, Honglai ; Xing, Lei ; Rossoll, Wilfried ; Wichterle, Hynek ; Singer, Robert H. ; Bassell, Gary J. / Multiprotein complexes of the survival of motor neuron protein SMN with Gemins traffic to neuronal processes and growth cones of motor neurons. In: Journal of Neuroscience. 2006 ; Vol. 26, No. 33. pp. 8622-8632.
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AU - Xing, Lei

AU - Rossoll, Wilfried

AU - Wichterle, Hynek

AU - Singer, Robert H.

AU - Bassell, Gary J.

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AB - Spinal muscular atrophy (SMA), a progressive neurodegenerative disease affecting motor neurons, is caused by mutations or deletions of the SMN1 gene encoding the survival of motor neuron (SMN) protein. In immortalized non-neuronal cell lines, SMN has been shown to form a ribonucleoprotein (RNP) complex with Gemin proteins, which is essential for the assembly of small nuclear RNPs (snRNPs). An additional function of SMN in neurons has been hypothesized to facilitate assembly of localized messenger RNP complexes. We have shown that SMN is localized in granules that are actively transported into neuronal processes and growth cones. In cultured motor neurons, SMN granules colocalized with ribonucleoprotein Gemin proteins but not spliceosomal Sm proteins needed for snRNP assembly. Quantitative analysis of endogenous protein colocalization in growth cones after three-dimensional reconstructions revealed a statistically nonrandom association of SMN with Gemin2 (40%) and Gemin3 (48%). SMN and Gemin containing granules distributed to both axons and dendrites of differentiated motor neurons. A direct interaction between SMN and Gemin2 within single granules was indicated by fluorescence resonance energy transfer analysis of fluorescently tagged and overexpressed proteins. High-speed dual-channel imaging of live neurons depicted the rapid and bidirectional transport of the SMN-Gemin complex. The N terminus of SMN was required for the recruitment of Gemin2 into cytoplasmic granules and enhanced Gemin2 stability. These findings provide new insight into the molecular composition of distinct SMN multiprotein complexes in neurons and motivation to investigate deficiencies of localized RNPs in SMA.

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