Gary J. Bassell

Associate Professor
Mechanisms and regulation of mRNA transport to growth cones and synapses of hippocampal neurons; Fragile-X mental retardation; Spinal Muscular Atrophy

Kennedy Center
Room 529
(718) 430-3640
bassell@aecom.yu.edu

 

Role of mRNA binding proteins in the regulation of axonal growth and synaptic plasticity; their dysfunction in Spinal Muscular Atrophy and Fragile X Mental Retardation

The major interest of our laboratory is to elucidate the function of mRNA binding proteins and associated protein complexes in the dynamic process of mRNA transport and local translation in neurons. We propose that two inherited diseases, Spinal Muscular Atrophy (SMA) and Fragile X Syndrome result from mutations or deletions that impair mRNA localization and/or translation. We have recently shown that mutations in SMA can impair the trafficking of SMN and result in defects in growth cone motility and neurite outgrowth. Future work will be to isolate the SMN complex in developing axons and identify the specific RNA targets. These studies will be important for potential therapeutic modalities that might restore their function in SMA. Our research on hippocampal neurons has identified a glutamatergic signaling pathway that regulates the dendritic trafficking of the Fragile X protein (FMRP) and we are beginning to assess possible defects in mRNA localization and synaptic protein synthesis in an FMR1 knockout mouse model. A third protein under study is zipcode binding protein (ZBP1), which binds and rapidly transports beta-actin mRNA in axons to the growth cones, in response to neurotrophin signaling. Ongoing research is aimed at understanding how ZBP1 is coupled to molecular motors. Our research utilizes a multi-disciplinary approach involving cellular, molecular and biochemical approaches to study the function of RNA-protein interactions in vitro and vivo.

 

Selected Publications

Antar,L.N., Afroz, R., Dictenberg, J.B., Carroll, R.C. and Bassell, G.J. Metabotropic glutamate receptor activation regulates Fragile X Mental Retardation Protein and Fmr1 mRNA localization differentially in dendrites and at synapses. Journal of Neuroscience, 2004; 24:2468-2655.

Eom, T., Antar, L. N., Singer, R. H., and Bassell, G. J. (2003). Localization of a beta-actin mRNP complex with zipcode binding protein modulates the density of dendritic filopdia and filopodial synapses. Journal of Neuroscience, 2003; 23:10433-10444.

Zhang, H. L., Pan, F., Hong, D., Shenoy, S. M., Singer, R. H., and Bassell, G. J. (2003). Active transport of the survival motor neuron protein and the role of exon-7 in cytoplasmic localization. J Neurosci 23, 6627-6637.

Tiruchinapalli, D. M., Oleynikov, Y., Kelic, S., Shenoy, S. M., Hartley, A., Stanton, P. K., Singer, R. H., and Bassell, G. J. (2003). Activity-dependent trafficking and dynamic localization of zipcode binding protein 1 and beta-actin mRNA in dendrites and spines of hippocampal neurons. J Neurosci 23, 3251-3261.

Zhang, H. L., Eom, T., Oleynikov, Y., Shenoy, S. M., Lieblet, D. A., Dictenberg, J. B., Singer, R. H., and Bassell, G. J. (2001). Neurotrophin induced transport of beta-actin mRNP complex increases beta-actin levels and stimulates growth cone motility. Neuron 31, 261-275.