Molecular mechanisms of myelin related disorders

Myelin sheaths are vital for a fast conduction of nerve impulses along the axons, facilitating a wide range of motor, sensory and cognitive functions.

Project information

Project duration

-

Project coordinator

University of Oulu

Contact information

Project leader

  • Postdoctoral researcher
    Salla Ruskamo

Project description

Myelin sheaths are vital for a fast conduction of nerve impulses along the axons, facilitating a wide range of motor, sensory and cognitive functions. Myelin is formed by oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. These cells wrap their plasma membrane around the neuronal axons and form a lipid-rich, multilamellar membrane structure. Myelin also consists of a unique set of proteins involved in the myelin formation and maintenance. Most myelin-specific proteins are either integral membrane proteins or otherwise closely linked to lipids.

Our lab studies the structural properties of the myelin-specific proteins and their ability to bind and reorganize lipids. We are also interested in the molecular level pathomechanisms of inherited disorders that affect myelin sheaths. Our methodology includes biophysical, biochemical and imaging techniques, such as X-ray crystallography, small-angle X-ray and neutron scattering, circular dichroism, atomic force microscopy, electron microscopy and biochemical protein interaction assays.

For more information, please see our research group home page: http://www.uib.no/en/rg/petrikursula

Project results

Selected publications:

Ponna SK, Ruskamo S, Myllykoski M, Keller C, Boeckers TM, Kursula P. (2018) Structural basis for PDZ domain interactions in the post-synaptic density scaffolding protein Shank3. J Neurochem. doi: 10.1111/jnc.14322.

Ruskamo S, Nieminen T, Kristiansen CK, Vatne GH, Baumann A, Hallin EI, Raasakka A, Joensuu P, Bergmann U, Vattulainen I, Kursula P. (2017) Molecular mechanisms of Charcot-Marie-Tooth neuropathy linked to mutations in human myelin protein P2. Sci Rep. 7(1):6510. doi: 10.1038/s41598-017-06781-0.

Raasakka A, Ruskamo S, Kowal J, Barker R, Baumann A, Martel A, Tuusa J, Myllykoski M, Bürck J, Ulrich AS, Stahlberg H, Kursula P. (2017) Membrane Association Landscape of Myelin Basic Protein Portrays Formation of the Myelin Major Dense Line. Sci Rep. 7(1):4974. doi: 10.1038/s41598-017-05364-3.

Tuusa J, Raasakka A, Ruskamo S and Kursula P. (2017) Myelin-derived and putative molecular mimic peptides share structural properties in aqueous and membrane-like environments. Multiple Sclerosis and Demyelinating Disorders 2:4. doi: 10.1186/s40893-017-0021-7.

Zenker J, Stettner M, Ruskamo S, Domènech-Estévez E, Baloui H, Médard JJ, Verheijen MH, Brouwers JF, Kursula P, Kieseier BC, Chrast R. (2014). A role of peripheral myelin protein 2 in lipid homeostasis of myelinating Schwann cells. Glia. 62(9):1502-12. doi: 10.1002/glia.22696.

Ruskamo S., Yadav RP, Sharma S, Lehtimäki M, Laulumaa S, Aggarwal S, Simons M, Bürck J, Ulrich AS, Juffer AH, Kursula I, Kursula P. (2014). Atomic resolution view into the structure-function relationships of the human myelin peripheral membrane protein P2. Acta Crystallogr. D Biol. Crystallogr. 70, 165-76. doi: 10.1107/S1399004713027910.

Ruskamo S., Chukhlieb M., Vahokoski J., Bhargav S.P., Liang F., Kursula I. And Kursula P. (2012) Juxtanodin is an intrinsically disordered F-actin binding protein. Sci Rep. 2:899. doi: 10.1038/srep00899.