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Dr. Alaa El-Husseini

  • Associate Professor, The Brain Centre, Dept. Psychiatry

  • Ph.D., Neuroscience (University of British Columbia)

  • Postdoctoral training at UCSF (David Bredt)
  • Research Objectives:

    Mechanisms that control synapse development

    Brain function relies on communication between nerve cells through highly specialized junctions known as synapses where one neuron can release a transmitter to pass on a signal to the another cell. In humans, the majority of synapses form during early prenatal and postnatal development until about 1 year after birth. By the end of this period, the 100 billion neurons in the brain have each formed thousands of synapses. However, it is unclear how an arriving axon selects a particular postsynaptic partner, how pre- and postsynaptic proteins are recruited to the initial site of contact to form a functional synapse, and how synapse stability is maintained. By using molecular tools to identify and manipulate components of the synaptic machinery, research in the laboratory is focused on elucidating mechanisms that underlie the establishment and maturation of synapses.

    Protein Complexes at Excitatory Synapses. (A) An image of a neuron stained with the presynaptic marker synaptophysin (green), to identify synaptic contacts. This panel illustrates steps involved in the assembly of proteins at contact sites.  Synapse formation is generally thought to involve three basic steps which include production of proteins in the cell soma (A-1), transport of these proteins to early sites of contact between axons and dendrites (A-2), and assembly of protein complexes at synapses (A-3).  (B, C) The intense clustering of proteins seen at the PSD of excitatory synapses is highlighted in the electron micrograph shown in B.  A schematic diagram of this region is blown up in C, illustrating the role of scaffolding molecules such as PSD-95 in assembly of large protein complexes. PSD-95 forms the core of the protein network, which is associated with the membrane through palmitoylation, and anchored within the postsynaptic compartment by several proteins that associates with actin. Coupling of PSD-95 to adhesion molecules such as neuroligins allows for trans-synaptic signaling.

    For more information on research projects in the lab, please visit the Projects page.

    If you'd like to contact members in the lab, please visit our Personnel page.

    Selected references:

    Yanai A, Huang K, Kang R, Singaraja RR, Arstikaitis P, Gan L, Orban PC, Mullard A, Cowan CM, Raymond LA, Drisdel RC, Green WN, Ravikumar B, Rubinsztein DC, El-Husseini A, Hayden MR. (2006). Palmitoylation of huntingtin by HIP14 is essential for its trafficking and function. Nat Neurosci 9, 824-831.

    Howarth, M., Chinnapen, D. J., Gerrow, K., Dorrestein, P. C., Grandy, M. R., Kelleher, N. L., El-Husseini, A., and Ting, A. Y. (2006). A monovalent streptavidin with a single femtomolar biotin binding site. Nat Methods 3, 267-273.

    Gerrow, K., Romorini, S., Nabi, S. M., Colicos, M. A., Sala, C., and El-Husseini, A. (2006). A preformed complex of postsynaptic proteins is involved in excitatory synapse development. Neuron 49, 547-562.

    Lise, M. F., Wong, T. P., Trinh, A., Hines, R. M., Liu, L., Kang, R., Hines, D. J., Lu, J., Goldenring, J. R., Wang, Y. T., and El-Husseini, A. (2006). Involvement of Myosin Vb in glutamate receptor trafficking. J Biol Chem 281, 3669-3678.

    Levinson, J. N., Chery, N., Huang, K., Wong, T. P., Gerrow, K., Kang, R., Prange, O., Wang, Y. T., and El-Husseini, A. (2005). Neuroligins Mediate Excitatory and Inhibitory Synapse Formation: involvement of PSD-95 and neurexin-1{beta} in neuroligin-induced synaptic specificity. J Biol Chem 280, 17312-17319.

    Huang, K., Yanai, A., Kang, R., Arstikaitis, P., Singaraja, R. R., Metzler, M., Mullard, A., Haigh, B., Gauthier-Campbell, C., Gutekunst, C. A., et al. (2004). Huntingtin-Interacting Protein HIP14 Is a Palmitoyl Transferase Involved in Palmitoylation and Trafficking of Multiple Neuronal Proteins. Neuron 44, 977-986.

    Prange, O., Wong, T. P., Gerrow, K., Wang, Y. T., and El-Husseini, A. (2004). A balance between excitatory and inhibitory synapses is controlled by PSD-95 and neuroligin. PNAS 101, 13915-13920.

    Kang, R., Swayze, R., Lise, M. F., Gerrow, K., Mullard, A., Honer, W. G., and El-Husseini, A. (2004). Presynaptic trafficking of synaptotagmin I is regulated by protein palmitoylation. J Biol Chem 279, 50524-50536.

    Gauthier-Campbell, C., Bredt, D. S., Murphy, T. H., and El-Husseini, A. E.-D. (2004). Regulation of Dendritic Branching and Filopodia Formation in Hippocampal Neurons by Specific Acylated Protein Motifs. Mol Biol Cell 15, 2205-2217.

    Swayze, R. D., Lise, M.-F., Levinson, J. N., Phillips, A., and El-Husseini, A. (2004). Modulation of dopamine mediated phosphorylation of AMPA receptors by PSD-95 and AKAP79/150. Neuropharmacology 47, 764-778.

    El-Husseini A. E., Schnell, E., Dakoji, S., Sweeney, N., Zhou, Q., Prange, O., Gauthier-Campbell, C., Aguilera-Moreno, A., Nicoll, R. A., and Bredt, D. S. (2002). Synaptic Strength Regulated by Palmitate Cycling on PSD-95. Cell 108, 849-863.

    El-Husseini, A. E., Schnell, E., Chetkovich, D. M., Nicoll, R. A., and Bredt, D. S. (2000). PSD-95 involvement in maturation of excitatory synapses. Science 290, 1364-1368.

    Select Reviews:

    Gerrow K. and El-Husseini A. (2006). Cell adhesion molecules at the synapse. Frontiers in Bioscience  11, 2400-2419.

    Lise MF and El-Husseini A. (2006). The neuroligin family:  structure and function during synapse development. Cell. Mol. Life Sci. In Press

    Huang, K., and El-Husseini, A. (2005). Modulation of neuronal protein trafficking and function by palmitoylation. Curr Opin Neurobiol 15, 527-535.

    Levinson, J. N., and El-Husseini, A. (2005). Building excitatory and inhibitory synapses: balancing neuroligin partnerships. Neuron 48, 171-174.



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