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

• Type of Material: Article
• Authors: Honglai Zhang, Albert Einstein College of Medicine; Le Xing, Emory University; Wilfried Rossoll, Emory University; Hynek Wichterle, Columbia University; Robert H. Singer, Albert Einstein College of Medicine; Gary Bassell, Emory University
• Language: English
• Date: 2006-08-16
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Final Published Version
• Copyright Statement: © 2006 Society for Neuroscience
• Final Published Version (URL): http://dx.doi.org/10.1523/JNEUROSCI.3967-05.2006
• Title of Journal or Parent Work: Journal of Neuroscience Nursing
• ISSN: 0888-0395
• Volume: 26
• Issue: 33
• Start Page: 8622
• End Page: 8632
• Grant/Funding Information: This work was supported by grants from the Spinal Muscular Atrophy Foundation, the Ritter Foundation, the Muscular Dystrophy Association, and Families of SMA.
• Keywords: CYTOPLASMIC LOCALIZATION; SPINAL MUSCULAR-ATROPHY; NEUROSCIENCES; CELLS; mRNA localization; BETA; growth cone; ZIPCODE-BINDING PROTEIN; Neurosciences; Science & Technology; Neurosciences & Neurology; RESONANCE ENERGY-TRANSFER; DETERMINING GENE-PRODUCT; spinal muscular atrophy; Life Sciences & Biomedicine; survival of motor neuron protein; STRESS GRANULES; SMN; ACTIN MESSENGER-RNA; motor neuron disease; SMA; RNA granules; SNRNP BIOGENESIS
• Research Categories: Biology, Neuroscience; Biology, Cell; Health Sciences, Pathology

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. Copyright © 2006 Society for Neuroscience.