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Author Notes:

Gary J. Bassell, Ph.D. Emory University School of Medicine Department of Cell Biology Whitehead Biomedical Research Bld. #415 615 Michael St. Atlanta, GA 30322 Tel.: (404)-727-3772 FAX: (404)-727-0570 gbassel@emory.edu

Wilfried Rossoll, Ph.D. Emory University School of Medicine Department of Cell Biology Whitehead Biomedical Research Bld. #415 615 Michael St. Atlanta, GA 30322 Tel.: (404)-727-0668 FAX: (404)-727-0570 wrossol@emory.edu

We thank Dr. Yukio Sasaki and Dr. Utz Fischer for providing antibodies.

We also thank Lian Li and Latoya Rowe for excellent technical support.

Subjects:

Research Funding:

This work was supported by SMA Europe fellowship to CF; Families of SMA grant to CF and WR; National Institutes of Health (NIH) grant NS066030 to WR; and NIH grant HD055835; Muscular Dystrophy Association grant 254779; and Spinal Muscular Atrophy Foundation to GJB.

We thank the Weisman Family Foundation for support of collaborative research (GJB, RHS).

The Neuronal Imaging Core is supported by Emory Neuroscience NINDS Core Facilities grant, P30NS055077.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Developmental Biology
  • Neurosciences
  • Neurosciences & Neurology
  • SMA
  • SMN
  • IMP1
  • axon
  • mRNA binding proteins
  • SPINAL MUSCULAR-ATROPHY
  • DETERMINING GENE-PRODUCT
  • GROWTH CONE GUIDANCE
  • BETA-ACTIN
  • LIVE CELLS
  • LOCALIZATION
  • DEFECTS
  • HUD
  • ZBP1
  • IDENTIFICATION

Dynamics of Survival of Motor Neuron (SMN) Protein Interaction with the mRNA-Binding Protein IMP1 Facilitates Its Trafficking into Motor Neuron Axons

Tools:

Journal Title:

Developmental Neurobiology

Volume:

Volume 74, Number 3

Publisher:

, Pages 319-332

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Spinal muscular atrophy (SMA) is a lethal neurodegenerative disease specifically affecting spinal motor neurons. SMA is caused by the homozygous deletion or mutation of the survival of motor neuron 1 (SMN1) gene. The SMN protein plays an essential role in the assembly of spliceosomal ribonucleoproteins. However, it is still unclear how low levels of the ubiquitously expressed SMN protein lead to the selective degeneration of motor neurons. An additional role for SMN in the regulation of the axonal transport of mRNA-binding proteins (mRBPs) and their target mRNAs has been proposed. Indeed, several mRBPs have been shown to interact with SMN, and the axonal levels of few mRNAs, such as the β-actin mRNA, are reduced in SMA motor neurons. In this study we have identified the β-actin mRNA-binding protein IMP1/ZBP1 as a novel SMN-interacting protein. Using a combination of biochemical assays and quantitative imaging techniques in primary motor neurons, we show that IMP1 associates with SMN in individual granules that are actively transported in motor neuron axons. Furthermore, we demonstrate that IMP1 axonal localization depends on SMN levels, and that SMN deficiency in SMA motor neurons leads to a dramatic reduction of IMP1 protein levels. In contrast, no difference in IMP1 protein levels was detected in whole brain lysates from SMA mice, further suggesting neuron specific roles of SMN in IMP1 expression and localization. Taken together, our data support a role for SMN in the regulation of mRNA localization and axonal transport through its interaction with mRBPs such as IMP1.

Copyright information:

© 2013 Wiley Periodicals, Inc.

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