Research Report 2000 - MDC

Tenascin-R modulates neurite
extension on F11 in vitro
F11 forms another subgroup of IgSF
recognition molecules that delineates
subpopulations of axons in the central
and peripheral nervous system and is
implicated in axonal fasciculation and
extension in vitro. In contrast to the
L1 subgroup of proteins, F11 and the
other members of this subclass are
anchored to the plasma membrane via
a glycosylphosphatidyl inositol (GPI)
moiety. F11 appears to exert its
function via interactions with multiple
heterophilic ligands, including other
IgSF members, tenascins and protein
tyrosine phosphatases. To gain insight
into how these interactions modulate
the activities of F11, we have
analyzed F11-mediated neurite
extension in the presence of tenascin-
R or tenascin-C in detail. Our studies
indicate that tenascin-R increases cell
attachment and neurite outgrowth on
immobilized F11. These tenascin-Rinduced
changes are accompanied by
a shift in receptor usage by tectal cells
from NrCAM to β1 integrins.
Furthermore, tenascin-R induces
morphological changes in tectal
neurons including enlargement of
growth cones and increased collateral
branching of neurites.
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IgLON subfamily: identification
of neurotractin
To examine the complex biology of
neural IgSF proteins further, we are
looking at the identification and
functional characterization of novel
members of this superfamily. Using a
systematic PCR approach, we have
identified a novel GPI-linked IgSF
member, termed neurotractin, that is
expressed on subsets of commissural
and longitudinal axon tracts in the
developing chick brain. Molecular
characterization indicates that
neurotractin is a member of the
IgLON subgroup of the IgSF which
has been created by the limbic
system-associated membrane protein
implicated in hippocampal circuit
formation. Its binding characteristics,
histological distribution together with
in vitro neurite outgrowth studies
suggest that neurotractin plays a role
in the development of central nervous
system axon tracts.
Figure 41: Schematic representation of the
homophilic L1 binding and heterophilic
interaction of L1 with F11 or axonin-1. Ig-like
domains (circles) and fibronectin-related
domains (ellipses) of L1, which carry diseaseassociated
mutations interferring with the
molecular interactions, are shown in blue (for
details please see De Angelis et al., 1999).
CALEB – a member of the EGF
family of differentiation factors
in the developing nervous
system
Another group of proteins implicated
in neuronal differentiation during
nervous system development are the
members of the EGF family of growth
and differention factors. By
combining binding assays with
immunological screening, we recently
identified a novel member of this
family, which we termed CALEB,
and which is expressed exclusively in
the nervous system. cDNA cloning
indicates that CALEB is a multidomain
protein that consists of an N-terminal
glycosylation region, a leucineproline-rich
segment, an acidic box, a
single EGF-like domain, a
transmembrane domain, and a short
cytoplasmic stretch. In the developing
nervous system, CALEB is associated
with glial and neuronal surfaces and is
downregulated in the adult nervous
system. CALEB binds to the
extracellular matrix glycoproteins,
tenascin-C and –R, and in vitro
antibody perturbation experiments
indicate the participation of CALEB
in neurite formation in a permissive
environment.