Poster abstracts
Poster number 78 submitted by Nikaela Losievski
The role of SRP54 in motor neuron development and implications for SMA
Nikaela Losievski (Department of Neuroscience, The Ohio State University), Pooja Kamath (Department of Biological Chemistry & Pharmacology, The Ohio State University), Amy Everest, PhD, Alan Kessler, PhD, Christine E. Beattie, PhD (Department of Neuroscience, The Ohio State University), Thomas L. Gallagher, PhD (Department of Molecular Genetics), Stephen J. Kolb, MD, PhD (Departments of Neuroscience and Biological Chemistry & Pharmacology), Sharon L. Amacher, PhD (Departments of Biological Chemistry & Pharmacology and Molecular Genetics)
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 an srp54-/- zebrafish line. Immunohistochemistry and confocal imaging will reveal if loss of Srp54 impacts motor axons and determine if an SMN:Srp54 association may contribute to motor neuron selectivity in SMA. This work will further the understanding of motor neuron selectivity in SMA and may provide insight into other motor neuron diseases.
Keywords: Signal recognition particle, Zebrafish, Motor neurons