@article {46708,
	title = {Dynamics of survival of motor neuron (SMN) protein interaction with the mRNA-binding protein IMP1 facilitates its trafficking into motor neuron axons.},
	journal = {Developmental Neurobiology},
	volume = {74},
	year = {2014},
	month = {2014 Mar},
	pages = {319-32},
	abstract = {<p>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.</p>
},
	keywords = {Animals, Axonal Transport, Axons, Biological Transport, Active, Brain, Cells, Cultured, Chromaffin Granules, Humans, Mice, Mice, Transgenic, Motor Neurons, Protein Interaction Domains and Motifs, Rats, RNA-Binding Proteins, Survival of Motor Neuron 1 Protein, Survival of Motor Neuron 2 Protein},
	issn = {1932-846X},
	doi = {10.1002/dneu.22111},
	author = {Fallini, Claudia and Rouanet, Jeremy P and Donlin-Asp, Paul G and Guo, Peng and Zhang, Honglai and Singer, Robert H and Rossoll, Wilfried and Bassell, Gary J}
}
@article {46738,
	title = {The survival of motor neuron (SMN) protein interacts with the mRNA-binding protein HuD and regulates localization of poly(A) mRNA in primary motor neuron axons.},
	journal = {The Journal of Neuroscience},
	volume = {31},
	year = {2011},
	month = {2011 Mar 9},
	pages = {3914-25},
	abstract = {<p>Spinal muscular atrophy (SMA) results from reduced levels of the survival of motor neuron (SMN) protein, which has a well characterized function in spliceosomal small nuclear ribonucleoprotein assembly. Currently, it is not understood how deficiency of a housekeeping protein leads to the selective degeneration of spinal cord motor neurons. Numerous studies have shown that SMN is present in neuronal processes and has many interaction partners, including mRNA-binding proteins, suggesting a potential noncanonical role in axonal mRNA metabolism. In this study, we have established a novel technological approach using bimolecular fluorescence complementation (BiFC) and quantitative image analysis to characterize SMN-protein interactions in primary motor neurons. Consistent with biochemical studies on the SMN complex, BiFC analysis revealed that SMN dimerizes and interacts with Gemin2 in nuclear gems and axonal granules. In addition, using pull down assays, immunofluorescence, cell transfection, and BiFC, we characterized a novel interaction between SMN and the neuronal mRNA-binding protein HuD, which was dependent on the Tudor domain of SMN. A missense mutation in the SMN Tudor domain, which is known to cause SMA, impaired the interaction with HuD, but did not affect SMN axonal localization or self-association. Furthermore, time-lapse microscopy revealed SMN cotransport with HuD in live motor neurons. Importantly, SMN knockdown in primary motor neurons resulted in a specific reduction of both HuD protein and poly(A) mRNA levels in the axonal compartment. These findings reveal a noncanonical role for SMN whereby its interaction with mRNA-binding proteins may facilitate the localization of associated poly(A) mRNAs into axons.</p>
},
	keywords = {Animals, Axons, Blotting, Western, Chick Embryo, Fluorescent Antibody Technique, HEK293 Cells, Hippocampus, Hu Paraneoplastic Encephalomyelitis Antigens, Humans, Immunoprecipitation, In Situ Hybridization, Fluorescence, Mice, Motor Neurons, Poly A, Poly(A)-Binding Proteins, Prosencephalon, Rats, SMN Complex Proteins},
	issn = {1529-2401},
	doi = {10.1523/JNEUROSCI.3631-10.2011},
	author = {Fallini, Claudia and Zhang, Honglai and Su, Yuehang and Silani, Vincenzo and Singer, Robert H and Rossoll, Wilfried and Bassell, Gary J}
}
