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A
Integrins
Test for Adhesion
CAMs
Cadherins
1
a
b
Laminin
Ca 2+
Fibronectin
B
Test for Growth
ECM
a
b
5
1
C
150
150
homophilic
homophilic
heterophilic
Integrins
FIGURE 5.19 Afew of the classes of adhesion molecules
expressed on the growth cone. Cadherins are calcium-dependent
homophilic adhesion molecules. Some members of the IgG super-
family of cell adhesion molecules, CAMs, can bind homophilically;
others are heterophilic. Integrins composed of various alpha and
beta subunits bind to a variety of different extracellular matrix com-
ponents with distinct affinity profiles.
100
100
50
50
0
0
L1
Polylysine
Cadherin
Laminin
FIGURE 5.18 Differential adhesion of growth cones. A. To quan-
titate adhesivity, a measured blast of culture medium is directed at
the growth cone. At a particular time, the growth cone becomes
detached. B. Growth is quantified by axon length increase over an
interval time. C. By using such tests, it can be shown that the class
of gray neurons has a different adhesion profile than the class of red
neurons. (After Lemmon et al., 1992)
cone as the specificity of integrin for particular ECM
proteins depends on the combination of a and b
subunits that are expressed (McKerracher et al., 1996).
There are 18 different a and 8 different b subunits,
and it is clear that different tissues, including different
neural tissues, use different subunit combinations. The
a5 subunit is particularly good at binding to fibronec-
tin, while the a6 subunit is better at binding to laminin.
Over the course of development, axons may change
which integrin subunits they express and thus change
their sensitivity to a particular ECM molecule. For
instance, chick retinal ganglion cells express a6 and
grow well on laminin when they are young. As they
mature, they stop expressing this subunit and lose their
ability to respond to laminin just as their axons make
contact with the tectum (Cohen and Johnson, 1991).
Many molecules that are excellent supporters of
axon growth have been isolated from the extracellular
matrix (ECM) (Bixby and Harris, 1991). These factors
were initially purified from culture media that was
conditioned by cells known to support axonal out-
growth. Some of the most abundant proteins in ECM,
such as laminin, fibronectin, vitronectin, and various
forms of collagen, all promote axon outgrowth. Many
of these ECM proteins are large and have many differ-
ent functional domains for cell attachment, for collagen
attachment, and for protein interactions. Different
neurons seem to show a preference for particular ECM
molecules. Vertebrate CNS cells grow particularly well
on laminin, while peripheral neurons often seem to
grow better on fibronectin. In experiments where
retinal neurons are given a choice between laminin and
fibronectin laid down in alternate stripes, retinal axons
clearly prefer laminin, though they will grow on either
substrate if given no choice.
Integrin is a receptor for many different extracellu-
lar matrix proteins, and it is composed of two subunits,
a and b (Figure 5.19). The extracellular matrix mole-
cule that an axon will respond to is largely a matter
of which integrin molecules are found at the growth
WHAT PROVIDES DIRECTIONAL
IN FORMATION TO GROWTH CON ES?
It has been suggested that four types of molecular
cues influence the direction in which growth cones will
travel (Tessier-Lavigne and Goodman, 1996). These are
divided into short-range and long-range cues, each
of which may be either attractive or repulsive (Figure
5.20). (1) Contact adhesion: a sudden increase in the
adhesivity of one cellular substrate compared to
another may cause axons to switch pathways; (2)
 
 
 
 
 
 
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