Oligodendroglial Cell Biology and CNS Myelination

Myelin in the central nervous system (CNS) is essential for normal nervous system development and function. Multiple sclerosis (MS) is the #1 neurological disease that afflicts young adults and results in targeted destruction of myelin, oligodendrocytes, and eventually, neurons in the CNS. Oligodendrocytes in the CNS serve to synthesize and maintain myelin sheaths, which are highly complex, multilamellar membranous structures essential to normal nervous system function. Myelination is a tightly regulated event that must occur during perinatal and early postnatal CNS development in vertebrates. Disruption of myelination during development can lead to mental retardation, movement disorders, and other neurological deficits.

Our research efforts focus on gaining a better understanding of the molecular and cellular biology of oligodendrocytes and the process of myelination. Our studies consider issues of cell polarity and membrane targeting for the distribution of proteins on the oligodendroglial cell surface and myelin membrane surrounding neurons. In particular, we are studying myelin/oligodendrocyte glycoprotein (MOG), which is specifically targeted for immune attack in MS. Our structure-function analyses of MOG have revealed sequence motifs in the cytoplasmic domain of this protein that are necessary for its membrane targeting and its ability to undergo endocytosis for reuptake back into the cell. Recently, we identified stathmin, a phosphoregulatory protein affecting microtubule dynamics, as a cytosolic binding partner for MOG, and we are now investigating the significance of these interactions. Surprisingly, the human MOG gene expresses alternatively spliced mRNAs that are translated to unique isoforms lacking these targeting and endocytic motifs. These novel MOG isoforms found in human CNS may exhibit altered developmental expression and may interact with alternative cytosolic partners. Studies in these areas are ongoing. We utilize an array of techniques encompassing cell biology, molecular biology, and protein chemistry. We hope that our efforts will aid in designing improved therapies for MS and myelin-related developmental neurological disorders.

Representative Publications:

Allamargot C. and Gardinier M.V. Alternative isoforms of myelin/oligodendrocyte dlycoprotein with variable cytoplasmic domains are expressed in human brain. J. Neurochem 101:298-312, 2007.

Kroepfl J.F. and Gardinier M.V. Mutually exclusive apico-basolateral sorting of two oligodendroglial membrane proteins, PLP and MOG, in MDCK cells. J Neurosci Res 66:1140-1148, 2001.

Kroepfl J.F. and Gardinier M.V. Identification of a basolateral membrane targeting signal within the cytoplasmic domain of myelin/oligodendrocyte. J Neurochem 77:1301-1309, 2001.

Click here to see a list of additional publications

Center and Program affiliations:

The Medical Scientist Training Program

Interdisciplinary Graduate Program in Molecular & Cellular Biology

Interdisciplinary Graduate Program in Neuroscience

Biosciences Program

Meeting Links:

ASCB - American Society for Cell Biology

ASN – American Society for Neurochemistry

GLG – Great Lakes Glia (Oct. 2009 – Traverse City, MI)

SFN – Society for Neuroscience

More complete information may be obtained at my Community of Science page.