Shasta Sabo, Ph.D.
Assistant Professor of Pharmacology
Phone: 368-5683
Fax: 368-1300
E-mail: shasta.sabo@case.edu
SOM W305C
Research
Formation of synapses between CNS neurons is a complex process that establishes the circuits that govern perception and behavior. Despite the importance of proper synapse formation for brain development and function, fundamental questions about the mechanisms of CNS synaptogenesis remain unanswered. For example, how are the protein complexes and specialized membrane domains critical for synaptic transmission assembled at the right place at the right time? Which proteins are essential for synapse development? How are pre- and post-synaptic assembly coordinated? Are the mechanisms of excitatory and inhibitory synapse formation similar? How is the balance of excitatory and inhibitory inputs onto a neuron controlled? Dr. Sabo’s research aims to address such questions.
To study synaptogenesis, Dr. Sabo uses live fluorescence imaging of postnatal rodent cortical neurons complemented with biochemical and molecular genetic approaches. Time-lapse imaging is powerful since it allows simultaneous study of spatial and temporal aspects of synapse formation and permits the observation and manipulation of individual synapses and networks in real-time, as they form. Approaches used to identify novel molecules important for synaptogenesis include testing mammalian orthologs of proteins identified in genetic model organisms and conducting genetic screens using RNAi. The roles of individual candidate proteins are studied using genetic and pharmacological manipulations.
These studies will have broad medical relevance since errors in synapse formation can have devastating functional implications: abnormal cortical synaptic connectivity has been linked to diseases as diverse as autism, mental retardation, amblyopia, epilepsy and schizophrenia. Understanding the normal choreography of synaptogenesis will be essential for understanding the etiology of such diseases.
Selected References:
Sabo SL, El-Sabeawy F and McAllister AK. JNK Controls Synaptogenesis by Regulating Synaptic
Vesicle Protein Trafficking to Nascent Synapses. In preparation.
Ikin AF, Sabo SL, Lanier LM, Buxbaum JD. A Macromolecular Complex Involving the Amyloid
Precursor Protein (APP) and the Cytosolic Adapter FE65 is a Negative Regulator of Axon Branching. In review at The Journal of Neuroscience.
Sabo SL, Gomes PR and McAllister AK. Formation of Presynaptic Terminals at Predefined Sites
Along Axons. The Journal of Neuroscience. In press (Oct. 18th issue). 2006.
-- highlighted in The Journal of Neuroscience “This Week in the Journal”
Gomes PR, Hampton CA, El-Sabeawy F, Sabo SL, McAllister AK. The Dynamic Localization of
TrkB Receptors Before, During and After Synapse Formation. The Journal of Neuroscience. In press. 2006.
Sabo SL and Sceniak MP. Somatostatin diversity in the Inhibitory Population. The Journal of
Neuroscience. 26(29): 7545-7546. 2006.
Sabo SL and McAllister AK. Mobility and Cycling of Synaptic Protein-Containing Vesicles in Axonal
Growth Cone Filopodia. Nature Neuroscience. 6(12): 1264-9. 2003.
-- highlighted in Faculty of 1000 and in Nature Cell Biology
Sabo SL, Ikin AF, Buxbaum JD, Greengard P. The Amyloid Precursor Protein and its Regulatory
Protein, FE65, in growth cones and nerve terminals in vitro and in vivo. The Journal of Neuroscience. 23(13): 5407-5415. 2003.
Sabo SL and Ikin AF. Cytoplasmic Protein-Protein Interactions that Regulate the Amyloid
Precursor Protein. Drug Development Research. 56(3): 228-241. 2002.
Sabo SL, Ikin AF, Buxbaum JD, Greengard P. The Alzheimer Amyloid Precursor Protein and
FE65, an APP-binding protein, Regulate Cell Movement. The Journal of Cell Biology. 153: 1403-1414. 2001.
-- highlighted in Alzheimer research forum, Trends in Pharmacology, and The Journal of Cell Biology
Sabo SL, Lanier L, Ikin AF, Khorkova O, Sahasrabudhe S, Greengard P, Buxbaum JD. Regulation
of beta-Amyloid Secretion by FE65, an Amyloid Protein Precursor-Binding Protein. Journal of Biological Chemistry. 274(12): 7952-7957. 1999.
Buxbaum JD, Ikin A, Luo Y, Naslund J, Sabo SL, Watanabe T, Greengard P. APP Localization and
Trafficking in the Central Nervous System. Progress in Alzheimer’s and Parkinson’s Disease. Plenum Press, New York. pp. 487-494. 1998.
Buxbaum JD, Ikin A, Luo Y, Naslund J, Sabo SL, Watanabe T, Greengard P. Regulation of APP Metabolism by Protein Phosphorylation. Progress in Alzheimer’s and Parkinson’s
Disease. Plenum Press, New York. pp. 133-140.1998.
Zambrano N, Buxbaum JD, Minopoli G, Fiore F, DeCandia P, De Renzis S, Faraonio R, Sabo SL, Cheetham J, Sudol M, Russo T. Interaction of the Phosphotyrosine Interaction/Phosphotyrosine Binding-related Domains of FE65 with Wild-type and Mutant beta-Amyloid Precursor Proteins. Journal of Biological Chemistry. 272 (10):
6399-6405. 1997.
Sabo SL, Lambert MP, Kessey K, Wade W, Krafft G, Klein WL. Interaction of beta-Amyloid Peptides with Integrins in a Human Nerve Cell Line. Neuroscience Letters. 184(1): 25-28.
1995.
Lambert MP, Sabo SL, Zhang C, Enam SA, Klein WL. Constitutive Alzheimer’s-Type Tau Epitopes in a Neuritogenic Rat CNS Cell Line. Neurobiology of Aging. 16(4): 583-589. 1995.
Lambert MP, Stevens G, Sabo SL, Barber K, Wang G, Wade W, Krafft G, Snyder S, Holzman TF, Klein WL. Beta/A4-Evoked Degeneration of Differentiated SH-SY5Y Human
Neuroblastoma Cells. Journal of Neuroscience Research. 39(4): 377-85. 1994.