The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Interaction of survival of motor neuron (SMN) and HuD proteins with mRNA cpg15 rescues motor neuron axonal deficits
Open accessAbstract
Spinal muscular atrophy (SMA), caused by the deletion of the SMN1 gene, is the leading genetic cause of infant mortality. SMN protein is present at high levels in both axons and growth cones, and loss of its function disrupts axonal extension and pathfinding. SMN is known to associate with the RNA-binding protein hnRNP-R, and together they are responsible for the transport and/or local translation of β-actin mRNA in the growth cones of motor neurons. However, the full complement of SMN-interacting proteins in neurons remains unknown. Here we used mass spectrometry to identify HuD as a novel neuronal SMN-interacting partner. HuD is a neuron-specific RNA-binding protein that interacts with mRNAs, including candidate plasticity-related gene 15 (cpg15). We show that SMN and HuD form a complex in spinal motor axons, and that both interact with cpg15 mRNA in neurons. CPG15 is highly expressed in the developing ventral spinal cord and can promote motor axon branching and neuromuscular synapse formation, suggesting a crucial role in the development of motor axons and neuromuscular junctions. Cpg15 mRNA previously has been shown to localize into axonal processes. Here we show that SMN deficiency reduces cpg15 mRNA levels in neurons, and, more importantly, cpg15 overexpression partially rescues the SMN-deficiency phenotype in zebrafish. Our results provide insight into the function of SMN protein in axons and also identify potential targets for the study of mechanisms that lead to the SMA pathology and related neuromuscular diseases.
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“Importantly, overexpression of HuD or of one of its target mRNAs (cpg-15) was found to partially rescue SMA-like defects related to cell morphology and recruitment of specific mRNAs into RNA granules (Hubers et al. 2010; Akten et al. 2011).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Akten et al. 2011
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“A series of cell imaging and biochemical experiments in three independent studies demonstrated that HuD interacts with SMN protein in axonal compartments of neurons (Hubers et al. 2010; Akten et al. 2011; Fallini et al. 2011).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Akten et al. 2011
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Correlation between severity and SMN protein level in spinal muscular atrophy
Lefebvre, S., Burlet, P., Liu, Q., Bertrandy, S., Clermont, O., Münnich, A., Dreyfuss, G., & Melki, J. (1997) · Nature Genetics · doi:10.1038/ng0797-265 · Cited by 1,100
Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick?
Burghes, A. H. M., & Beattie, C. E. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2670 · Cited by 723
Self-citationRossoll, W., Jablonka, S., Andreassi, C., Kröning, A.-K., Karle, K. N., Monani, U. R., & Sendtner, M. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200304128 · Cited by 637
Diverse molecular functions of Hu proteins
Hinman, M. N., & Lou, H. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8252-6 · Cited by 587
Plastin 3 Is a Protective Modifier of Autosomal Recessive Spinal Muscular Atrophy
Oprea, G. E., Kröber, S., McWhorter, M. L., Rossoll, W., Müller, S., Krawczak, M., Bassell, G. J., Beattie, C. E., & Wirth, B. (2008) · Science · doi:10.1126/science.1155085 · Cited by 496
Self-citationMcWhorter, M. L., Monani, U. R., Burghes, A. H. M., & Beattie, C. E. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200303168 · Cited by 423
Self-citationFlanagan‐Steet, H. R., Fox, M. A., Meyer, D., & Sanes, J. R. (2005) · Development · doi:10.1242/dev.02044 · Cited by 345
Axonal mRNA in Uninjured and Regenerating Cortical Mammalian Axons
Taylor, A. M., Berchtold, N. C., Perreau, V. M., Tu, C. H., Jeon, N. L., & Cotman, C. W. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.6130-08.2009 · Cited by 328
Rossoll, W. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.1.93 · Cited by 291
Gubitz, A. K. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.03.022 · Cited by 277
Zhang, H. L., Pan, F., Hong, D., Shenoy, S. M., Singer, R. H., & Bassell, G. J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-16-06627.2003 · Cited by 273
Extracellular stimuli specifically regulate localized levels of individual neuronal mRNAs
Willis, D. E., van Niekerk, E. A., Sasaki, Y., Mesngon, M. T., Merianda, T. T., Williams, G. G., Kendall, M., Smith, D. S., Bassell, G. J., & Twiss, J. L. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200703209 · Cited by 270
Self-citationTsc2-Rheb signaling regulates EphA-mediated axon guidance
Nie, D. A., Nardo, A. D., Han, J. M., Baharanyi, H., Kramvis, I., Huynh, T., Dabora, S. L., Codeluppi, S., Pandolfi, P. P., Pasquale, E. B., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2477 · Cited by 243
Self-citationFallini, C., Zhang, H., Su, Y., Silani, V., Singer, R. H., Rossoll, W., & Bassell, G. J. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3631-10.2011 · Cited by 221
Promotion of Dendritic Growth by CPG15, an Activity-Induced Signaling Molecule
Nedivi, E., Wu, G., & Cline, H. T. (1998) · Science · doi:10.1126/science.281.5384.1863 · Cited by 210
Zhang, H., Xing, L., Rossoll, W., Wichterle, H., Singer, R. H., & Bassell, G. J. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3967-05.2006 · Cited by 200
Pascale, A., Gusev, P. A., Amadio, M., Dottorini, T., Govoni, S., Alkon, D. L., & Quattrone, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307674100 · Cited by 174
Postsynaptic CPG15 promotes synaptic maturation and presynaptic axon arbor elaboration in vivo
Cantallops, I., Haas, K. Z., & Cline, H. T. (2000) · Nature Neuroscience · doi:10.1038/79823 · Cited by 165
Carrel, T. L., McWhorter, M. L., Workman, E., Zhang, H., Wolstencroft, E. C., Lorson, C. L., Bassell, G. J., Burghes, A. H. M., & Beattie, C. E. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.1637-06.2006 · Cited by 165
Self-citationAtlas, R., Behar, L., Elliott, E., & Ginzburg, I. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02371.x · Cited by 152
Coordinated Motor Neuron Axon Growth and Neuromuscular Synaptogenesis Are Promoted by CPG15 In Vivo
Javaherian, A., & Cline, H. T. (2005) · Neuron · doi:10.1016/j.neuron.2004.12.051 · Cited by 148
Hubers, L., Valderrama-Carvajal, H., Laframboise, J., Timbers, J., Sanchez, G., & Côté, J. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddq500 · Cited by 138
Nedivi, E., Fieldust, S., Theill, L. E., & Hevron, D. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.5.2048 · Cited by 124
Soluble CPG15 expressed during early development rescues cortical progenitors from apoptosis
Putz, U., Harwell, C. C., & Nedivi, E. (2005) · Nature Neuroscience · doi:10.1038/nn1407 · Cited by 122
Bolognani, F., Contente-Cuomo, T., & Perrone-Bizzozero, N. I. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkp863 · Cited by 113
Glinka, M., Herrmann, T., Funk, N., Havlicek, S., Rossoll, W., Winkler, C., & Sendtner, M. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq073 · Cited by 105
The ELAV Protein HuD Stimulates Cap-Dependent Translation in a Poly(A)- and eIF4A-Dependent Manner
Fukao, A., Sasano, Y., Imataka, H., Inoue, K., Sakamoto, H., Sonenberg, N., Thoma, C., & Fujiwara, T. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.11.013 · Cited by 100
Wang, H., Dictenberg, J. B., Ku, L., Li, W., Bassell, G. J., & Feng, Y. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-06-0583 · Cited by 71
Dendritic LSm1/CBP80-mRNPs mark the early steps of transport commitment and translational control
di Penta, A., Mercaldo, V., Florenzano, F., Munck, S., Ciotti, M. T., Zalfa, F., Mercanti, D., Molinari, M., Bagni, C., & Achsel, T. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200807033 · Cited by 61
Lefebvre, S. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.9.1017 · Cited by 55
Activity-dependent expression of RNA binding protein HuD and its association with mRNAs in neurons
Tiruchinapalli, D. M., Ehlers, M., & Keene, J. D. (2008) · RNA Biology · doi:10.4161/rna.5.3.6782 · Cited by 54
Activity‐dependent expression of ELAV/Hu RBPs and neuronal mRNAs in seizure and cocaine brain
Tiruchinapalli, D. M., Caron, M. G., & Keene, J. D. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05718.x · Cited by 52
Identification of Novel Interacting Protein Partners of SMN Using Tandem Affinity Purification
Shafey, D., Boyer, J. G., Bhanot, K., & Kothary, R. (2010) · Journal of Proteome Research · doi:10.1021/pr9006987 · Cited by 43
Developmental regulation of CPG15 expression in Xenopus
Nedivi, E., Javaherian, A., Cantallops, I., & Cline, H. T. (2001) · The Journal of Comparative Neurology · doi:10.1002/cne.1044 · Cited by 40
SMN, Gemin2 and Gemin3 Associate with β-Actin mRNA in the Cytoplasm of Neuronal Cells In Vitro
Todd, A. G., Morse, R., Shaw, D. J., McGinley, S., Stebbings, H., & Young, P. J. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.06.058 · Cited by 37
HuD Regulates the cpg15 Expression Via the 3′-UTR and AU-Rich Element
Wang, Z., Li, S.-J., Qi, Y., Zhao, J., Liu, X.-Y., Han, Y., Xu, P., & Chen, X.-H. (2011) · Neurochemical Research · doi:10.1007/s11064-011-0443-0 · Cited by 22
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Singh, R. N., Howell, M. D., Ottesen, E. W., & Singh, N. N. (2017) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2016.12.008 · Cited by 325
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Metadata
- Authors
- Akten, B., Kye, M. J., Hao, L. T., Wertz, M. H., Singh, S., Nie, D., Huang, J., Merianda, T. T., Twiss, J. L., Beattie, C. E., Steen, J. A. J., & Sahin, M.
- Affiliations
- Boston Children's Hospital (US)
- The Ohio State University (US)
- Drexel University (US)
- The F.M. Kirby Neurobiology Center, Department of Neurology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115;
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-06-07
- Volume
- 108
- Issue
- 25
- Pages
- 10337-10342
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3121858
- OpenAlex
- W2013174632
- Cited by
- 203
- References
- 36
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 4 · 2023: 11 · 2022: 12 · 2021: 15 · 2020: 18 · 2019: 8 · 2018: 13 · 2017: 21 · 2016: 18 · 2015: 13 · 2014: 21 · 2013: 22 · 2012: 12
- FWCI
- 9.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Spinal Muscular Atrophy Foundation
- Hearst Foundations
- Harvard NeuroDiscovery Center
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS050414, R01 NS66973, NS 041596, R01NS050414, R01NS066973, R56NS050414, R01NS041596)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655, P30HD-18655)
- Topics
- Health Sciences › Medicine › Genetics (clinical) › Neurogenetic and Muscular Disorders Research
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- spinal muscular atrophy, SMN protein, HUD, RNA-binding proteins, motor neuron axons, axon branching, neuromuscular synapse formation
- MeSH terms
- ELAV-Like Protein 4, Animals, Axons, Cells, Cultured, Embryo, Mammalian, Humans, Motor Neurons, Nerve Tissue Proteins, Neuropeptides, Recombinant Fusion Proteins, RNA, Messenger, Zebrafish, Animals, Genetically Modified, Mice, ELAV Proteins, Survival of Motor Neuron 1 Protein, GPI-Linked Proteins
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