Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Interaction of survival of motor neuron (SMN) and HuD proteins with mRNA cpg15 rescues motor neuron axonal deficits.

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.

Pubmed ID: 21652774 RIS Download

Mesh terms: Animals | Animals, Genetically Modified | Axons | Cells, Cultured | ELAV Proteins | ELAV-Like Protein 4 | Embryo, Mammalian | GPI-Linked Proteins | Humans | Mice | Motor Neurons | Nerve Tissue Proteins | Neuropeptides | RNA, Messenger | Recombinant Fusion Proteins | Survival of Motor Neuron 1 Protein | Zebrafish

Research tools detected in this publication

None found

Data used in this publication

Associated grants

  • Agency: NINDS NIH HHS, Id: R01 NS66973
  • Agency: NINDS NIH HHS, Id: NS041596
  • Agency: NICHD NIH HHS, Id: P30 HD 18655
  • Agency: NINDS NIH HHS, Id: R56 NS050414
  • Agency: NINDS NIH HHS, Id: R01 NS066973
  • Agency: NICHD NIH HHS, Id: P30 HD018655
  • Agency: NINDS NIH HHS, Id: R01 NS050414
  • Agency: NINDS NIH HHS, Id: NS050414
  • Agency: NINDS NIH HHS, Id: R01 NS041596

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.