Stephen Lambert, Ph.D.

Academic Role: Assistant Professor

Faculty Appointment(s) In:
   Cell Biology

Other Affiliation(s):
   Cell Dynamics Group
   Interdisciplinary Graduate Program
   Program in Neuroscience

Membrane-Cytoskeleton Interactions in Axonal Function

The physiological activity of a wide variety of metazoan cell types depends in some part on the ability of these cells to segregate integral membrane proteins, such as receptors and ion channels, at high concentrations into specialized domains of the plasma membrane. Research in this laboratory focuses on the role of the spectrin-based membrane skeleton in the formation of specialized membrane domains in the nervous system. We are particularly interested in interactions that involve the ankyrins, a family of peripheral 'adapter' proteins that link integral proteins to the spectrin skeleton. The membrane domains that we focus on are the nodes of Ranvier. The nodes are 1um sized differentiated areas of the myelinated axonal membrane enriched in ion channels necessary for the formation of action potentials. These patches of 'excitable' membrane are regularly arranged along the length of the axon at gaps in the myelin sheath. The segregation of ion channels to the nodal membrane is crucial to the saltatory action potential of myelinated axons and the fast conduction velocity associated with these axons. It is also a factor in the pathology underlying human demyelinating diseases such as multiple sclerosis.

Recent research has identified a novel form of ankyrin as a component of the nodal membrane. Studies on the morphogenesis of the node indicate a key role for this molecule in the formation of the node by theoretically forming a multivalent complex with both cell adhesion molecules and ion channels. Future work in this area will be on further defining this protein complex, determining the role of glial cells in node formation and characterizing a 'knock-out' mouse, where this isoform of ankyrin is missing.

Figure Legend: Immunofluorescence localization of ankyrin_G, 480/270kDa (green), with respect to spectrin (red), at the node of Ranvier in the adult rat sciatic nerve.

Recent Publications

Kordeli, E., Lambert, S., Bennett, V. (1995) Ankyrin_G: a novel ankyrin gene with neural-specific isoforms localized at the axonal initial segment and node of Ranvier. J. Biol. Chem., 270:2352- 2359.

Lambert, S. and Bennett, V. (1996) Axonal ankyrins and ankyrin-binding proteins: potential participants in lateral membrane domains and transcellular connections at the node of Ranvier. In: "The plasma membrane-cytoskeleton interface: template for protein domains, vesicle trafficking and signal transduction." (W. James Nelson, ed), Academic Press, Orlando, pp 129-145.

Davis, J.Q., Lambert, S., Bennett, V. (1996) Molecular composition of the node of Ranvier: identification of ankyrin-binding cell adhesion molecules neurofascin (mucin+/third FNIII domain-) and NrCAM at nodal axon segments. J. Cell. Biol., 135:1355-1367.

Kaplan, M.R., Meyer-Franke, A., Lambert, S., Bennett, V., Duncan, I.D., Levinson, S.R., Barres, B.A. (1997) Induction of sodium channel clustering by oligodendrocytes. Nature, 386:724-728.

Lambert, S., Davis, J.Q., Bennett, V. Morphogenesis of the node of Ranvier: co-clusters of ankyrin and ankyrin-binding integral proteins define early developmental intermediates. J. Neurosci., in press.

Rotation Projects

No rotation projects are available at this time.

Academic Background

Ph.D., University of the Witwatersrand, Johannesburg, S. Africa, 1992

Office: Bioech4 Suite 326
E-mail: Stephen.Lambert@umassmed.edu
Keywords: Neurobiology, Cell Biology

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