Local translation and axon survival in touch sensation
Rosalind Segal, MD, Ph.D
Harvard Medical School
Host: Aram Raissi (Shatz Lab)
Axons provide the essential long-range connections that establish and maintain complex brain circuitry. However, the mechanisms that regulate axonal viability during development and throughout life are not well understood. We report that an RNA-binding protein, SFPQ, interacts with multiple mRNAs localized to axons of sensory neurons. SFPQ promotes the co-assembly of distinct mRNAs into transport granules destined for the Distal axons. Genetic reduction of SFPQ results in lower levels of target mRNAs in axons, and consequently causes axonal degeneration. Thus SFPQ is a key component of an RNA regulon responsible for neurotrophin-dependent axonal survival. SFPQ has been implicated in multiple neurologic disorders. Thus, our studies suggest that aberrations in post-transcriptional regulation of key axonal components promote degeneration during early stages of neurologic disease. Accordingly we examine the implications of these findings for degenerative disorders including chemotherapy induced peripheral neuropathy and for ALS.
 Paclitaxel Reduces Axonal Bclw to Initiate IP3R1-Dependent Axon Degeneration. Pease-Raissi SE, Pazyra-Murphy MF, Li Y, Wachter F, Fukuda Y, Fenstermacher SJ, Barclay LA, Bird GH, Walensky LD, Segal RA. Neuron. 2017 Oct 11. 96(2):373-386. PMCID: PMC5680044. DOI: http://dx.doi.org/10.1016/j.neuron.2017.09.034
 >• The RNA-binding protein SFPQ orchestrates an RNA regulon to promote axon viability. Cosker KE, Fenstermacher SJ, Pazyra-Murphy MF, Elliott HL, Segal RA. Nat Neurosci. 2016 May;19(5):690-696. PMCID: PMC5505173. doi:10.1038/nn.4280