Professor Emerita

Joan Boggs

Department of Laboratory Medicine & Pathobiology

BA, MSc, PhD

Hospital for Sick Children (SickKids)
555 University Ave., Room 3427C, Toronto, Ontario Canada M5G 1X8
Appointment Status

My research program is aimed at understanding myelinogenesis by oligodendrocytes. We are currently focusing on the structure and roles of myelin basic protein in interactions with the cytoskeleton and SH3-domain proteins and the role of glycosphingolipids in cell-surface phenomena. We are also studying the effect of estrogens on oligodendrocytes and myelin.


Research Synopsis


My research program is aimed at understanding structural mechanisms of cell membrane behaviour, particularly in oligodendrocytes. We are currently focusing on the structure and roles of myelin basic protein in interactions with the cytoskeleton and SH3-domain proteins and the role of glycosphingolipids in cell-surface phenomena. We study purified proteins, reconstituted model membranes, isolated myelin, cultured oligodendrocytes, and brain slices by a number of biochemical, biophysical, and cell biology techniques, including electron paramagnetic resonance spectroscopy (spin labeling), Cysteine-scanning and cysteine-specific labeling, in vitro protein-protein interactions and confocal microscopy of fluorescent-antibody-stained cells or cells transfected with DNA for fluorescent proteins.

We have shown that myelin basic protein (MBP) can interact with a number of other proteins in vitro. It can assemble actin filaments and microtubules, bundle them and bind them to a lipid bilayer and to each other.  It has an SH3-domain ligand motif and can bind to several proteins with SH3 domains and bind them to a lipid bilayer. Thus MBP could serve as a scaffolding protein and bind cytoskeletal and signaling proteins to the plasma membrane, in addition to its function in adhesion of the cytoplasmic surface of myelin. This binding can be regulated by post-translational modifications of MBP, deimination and phosphorylation, Ca2+-calmodulin binding (1), and the negative surface charge of the lipid bilayer. We are now investigating its ability to bind to these proteins in cells, the effect of post-translational modifications to MBP, and the role of this binding in cell function. 

Myelin is very rich in glycosphingolipids and we are investigating their role in cultured oligodendrocytes. We have shown that myelin glycosphingolipids can adhere to each other between apposed bilayers by carbohydrate-carbohydrate interactions. This interaction may occur between rafts in apposed bilayers in the multilayered myelin sheath or between apposed oligodendrocyte processes, thus forming “glycosynapses”, which convey extracellular signals to the cytosolic side. This interaction causes depolymerization of actin filaments and microtubules in the cells.

Recently, we discovered a membrane form of the estrogen receptor in oligodendrocytes and myelin and showed that it can trigger rapid signaling and phosphorylation of several kinases in oligodendrocytes.  Furthermore, 17α-estradiol, a form active on the membrane estrogen receptor in other cells but not on the nuclear receptor, also stimulated rapid signaling in oligodendrocytes. Since 17α-estradiol is produced in the brain of both males and females at even higher concentrations than 17β-estradiol, the form active on the nuclear receptor, it could play a role in myelination and have therapeutic potential for MS. We are studying the effect of estrogens on oligodendrocytes and myelination further using cultured oligodendrocytes and brain slices


Recent Publications


Boggs, J.M., Myelin Basic Protein: A Multifunctional Protein. Cell. Mol. Life Sci. 63 (2006) 1945-61. 

Boggs, J. M., Rangaraj, G., Gao, W., and Heng, Y-M., Effect of phosphorylation of myelin basic protein by MAPK on its interactions with actin and actin binding to a lipid membrane in vitro, Biochemistry 45 (2006) 391-401 

Musse, A. A., Boggs, J. M., and Harauz, G., Deimination of membrane-associated myelin basic protein in multiple sclerosis exposes an immunodominant epitope, Proc. Natl. Acad. Sci. U.S.A. 103 (2006) 4422-4427  co-SRA . 

Comment by C. Husted, Structural insight into the role of myelin basic protein in multiple sclerosis, pp. 4339-4340.

Boggs, J. M., Gao, W., and Hirahara Y., Myelin glycosphingolipids, galactosylceramide and sulfatide, participate in carbohydrate-carbohydrate interactions between apposed membranes and may form glycosynapses between oligodendrocyte and/or myelin membranes. Biochim. Biophys. Acta 1780 (2008) 445-455 . 

Polverini, E., Rangaraj, G., Libich, D., Boggs, J.M., and Harauz, G., Binding Of The Proline-Rich Segment Of Myelin Basic Protein To Sh3-Domains – Spectroscopic, Microarray, And Modelling Studies Of Ligand Conformation And Effects Of Post-Translational Modifications, Biochemistry 47 (2008) 267-282. 

Musse, A. A., Gao, W., Homchaudhuri, L., Boggs, J. M., and Harauz, G. Myelin Basic Protein as a "PI(4,5)P2-Modulin": A New Biological Function for a Major Central Nervous System Protein, Biochemistry 47 (2008) 10372-82. 

Culham, D. E., Vernikovska, Ya. I., Tschowri, N., Keates, R. A. B., Wood, J. M., and Boggs, J. M., Periplasmic loops of osmosensory transporter ProP in Escherichia coli are sensitive to osmolality, Biochemistry 47 (2008) 13584-13593.

Hirahara, Y., Matsuda, K-I., Gao, W., Arvanitis, D. N., Kawata, M., and Boggs, J. M., The localization and non-genomic function of the membrane-associated estrogen receptor in oligodendrocytes, Glia 57 (2009) 153-165.

Min, Y., Kristiansen, K., Boggs, J. M., Husted, C., Zasadizinski, J., and Israelachvili, J., Interaction forces and adhesion of supported myelin lipid bilayers modulated by myelin basic protein, Proc. Natl. Acad. Sci. U.S.A. 106 (2009) 3154-3159. 

Homchaudhuri, L., Polverini, E., Gao, W., Harauz, G., and Boggs, J. M., Influence of membrane surface charge and post-translational modifications to myelin basic protein on its ability to tether the Fyn-SH3 domain to a membrane, Biochemistry 48 (2009) 2385-2393. 

Homchaudhuri, L., De Avila, M., Nilsson, S., Bessonov, K., Smith, G., Bamm, V., Musse, A., Harauz, G., and Boggs, J.M., Secondary Structure and Solvent Accessibility of a Calmodulin-Binding C-Terminal Segment of Membrane-Associated Myelin Basic Protein. Biochemistry, 49 (2010) 8955-8966.

Smith, G.S.T., Paez, P. M., Spreuer, V., Campagnoni, C. W., Boggs, J. M., Campagnoni, A. T., and Harauz, G., Classic 18.5 and 21.5 kDa isoforms of myelin basic protein inhibit calcium influx into oligodendroglial cells, in contrast to golli isoforms, J. Neurosci. Res. 89 (2011) 467-480.

Smith, G.S.T., De Avila, Paez, P.M., Spreuer, V., M., Wills, M. K. B., Jones, N., Boggs, J. M., and Harauz, G., Proline substitutions and threonine pseudophosphorylation of the SH3-ligand of 18.5 kDa myelin basic protein decrease its affinity for the Fyn-SH3 domain and alter process development and protein localization in oligodendrocytes.  J. Neurosci. Res. 90 (2012) 28-47.

Smith, G. S. T., Homchaudhuri, L., Boggs, J. M., and Harauz, G., Classic 18.5-kDa and 21.5 kDa myelin basic protein isoforms associate with cytoskeletal and SH3-domain proteins in phorbol ester- and IGF-1-stimulated immortalized N19-oligodendroglial cells, Neurochem. Res. 37 (2012) 1277-1295.

Smith, G.S.T., Seymour, L. V., Boggs, J. M., and Harauz, G., The 21.5-kDa isoform of myelin basic protein has a non-traditional PY-nuclear localization signal, Biochem. Biophys. Res. Commun. 422 (2012) 670-675.