This laboratory has focused on a system of proteins
associated with plasma membranes of most animal cells
known as the spectrin-based membrane skeleton. Spectrin
and its associated proteins are candidates to localize
integral membrane proteins at specialized regions
of the plasma membrane. Examples of physiologically
important cell domains involving spectrin include
axons of neurons, the neuromuscular junction, nodes
of Ranvier and axon initial segments of myelinated
axons, and basolateral domains of epithelial cells.
Much of the work involves ankyrins, which are a family
of spectrin-binding proteins that link the spectrin
skeleton to multiple membrane proteins, adducin, a
PKC substrate and calmodulin-binding protein that
directs spectrin to the fast-growing end of actin
filaments, and beta spectrin which mediates most of
the protein interactions of the spectrin molecule.
Recent progress includes the discovery of a new ankyrin
gene encoding polypeptides expressed in a variety
of cells as well as an alternatively-spliced variant
that is localized at nodes of Ranvier and axon initial
segments of myelinated neurons as well as the neuromuscular
junction. We have recently discovered that a major
class of nervous system cell adhesion molecules, the
L1CAM family, contain binding sites for ankyrin and
include isoforms localized at the node of Ranvier.
Tyrosine phosphorylation of a conserved site in the
cytoplasmic domain of the L1CAM family abolishes ankyrin-binding
activity, and also abolishes ability to participate
in cell sorting. We are currently evaluating ankyrin
function in the nervous system and striated muscle
using gene knock-out of ankyrinB and ankyrinG in mice.
