Poster abstracts
Poster number 87 submitted by Nikaela Losievski
The role of Srp54 in motor neuron development in zebrafish and implications for spinal muscular atrophy
Nikaela Losievski (Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH), Pooja Kamath (Department of Biological Chemistry & Pharmacology, The Ohio State University Wexner Medical Center, Columbus, OH), Ashley Fox, Stephen J Kolb (Departments of Neurology and Biological Chemistry & Pharmacology, The Ohio State University Wexner Medical Center, Columbus, OH ), Amy Everest (Department of Molecular Genetics, The Ohio State University, Columbus, OH), Thomas L. Gallagher, Sharon L. Amacher (Departments of Biological Chemistry, Molecular Genetics, and Center for RNA Biology, The Ohio State University, Columbus, OH), Alan Kessler (Department of Neuroscience, The Ohio State University, Columbus, OH)
Abstract:
Spinal muscular atrophy (SMA) is a motor neuron disease typically caused by a mutation in or deletion of the SMN1 gene that reduces the amount of survival of motor neuron (SMN) protein throughout an organism. All cells require SMN to survive, but the first observed symptoms in SMA patients are motor neuron dysfunction and death. It is unknown why motor neurons are especially sensitive to deficient functional SMN protein. SMN oligomerizes to form the SMN complex whose canonical function is small nuclear ribonucleoprotein (snRNP) assembly. Additionally, SMN complex has been implicated in other RNP assembly processes that may contribute to motor neuron selectivity in SMA. To determine what SMN associations may be crucial to motor neuron health, we used a transgenic zebrafish that expresses tagged SMN protein under a motor neuron-specific promoter. Co-immunoprecipitation showed that Srp54 protein could associate with SMN specifically in motor neurons. Srp54 is a component of the signal recognition particle (SRP), an RNP that regulates the translation of a subset of secreted and integral membrane proteins. Previous work suggests that SMN promotes SRP biogenesis and stability in vitro. To test if loss of Srp54 affects motor axon morphology in zebrafish reminiscent of the SMA model, we assess axon morphology in a srp54-/- zebrafish line. Motor axons in srp54-/- embryos were shorter and less branched than those in their clutchmates. These defects precede multisystemic defects in srp54-/- which suggests motor neurons are more sensitive than other tissue types to deficient Srp54 protein levels, analogous to Smn. The proposed mechanism between SMN and Srp54 may be pertinent to motor neuron selectivity in SMA and may provide insight into other motor neuron diseases.
Keywords: Zebrafish, Motor neurons, Spinal muscular atrophy