Biology Reference
In-Depth Information
RCP construct localizes to the periphery of adult DRG growth cones,
where it colocalizes with surface-labeled
b
1 integrins, and functions to in-
crease their expression (
Eva et al., 2010
). Recycling endosomes marked by
Rab11 are therefore important for delivery of recycling integrins onto the
growth cone surface.
Growth cone advance does not rely on simple exocytosis of adhesionmol-
ecules, but relies on internalization and recycling which creates a balance be-
tween adhesion and release that allows for growth cone advance. This
hypothesis proposes that adhesion molecules link the actin cytoskeleton to
the ECM, andmove backwards with retrograde actin flowas the growth cone
advances, before being endocytosed and recycled via molecular motors to-
ward the front of the growth cone (
Itofusa&Kamiguchi, 2011
). This has been
directly demonstrated for L1/NgCAM in axonal growth cones of embryonic
chick DRG neurons (
Kamiguchi & Lemmon, 2000
), and embryonic hippo-
campal neurons (
Dequidt et al., 2007
).
b
1 integrins are endocytosed at the
growth cones of adult DRG neurons into Rab11 compartments, and these
compartments are enriched in the filopodia and peripheral domain of the
growth cone (
Eva et al., 2010
). Endocytosis of integrins is important for guid-
ance, as a gradient of the inhibitory molecule MAG induces polarized endo-
cytosis of
b
1 integrins on the exposed side of the growth cone, leading to
repulsive turning (
Hines et al., 2010
). Further, integrin-dependent point con-
tacts are redistributed in the direction of attractive signals generated by BDNF
application (
Myers & Gomez, 2011
). Polarized traffic across the axis of the
growth cone is central to growth cone steering, with polarized endocytosis
and exocytosis of membrane components required for both attractive and
repulsive cues (
Tojima et al., 2007, 2010
). Both the exocytic and endocytic
machinery are therefore required for growth cone formation and function.
At present, there is little consensus as to the mechanism by which
integrins are endocytosed, with some studies reporting that they can be in-
ternalized by clathrin-mediated endocytosis in nonneuronal cells and at the
growth cone (
Arjonen et al., 2012; Ezratty et al., 2009; Hines et al., 2010
),
while others report internalization independently of clathrin via caveolin
(
Bass et al., 2011; Brown, Rozelle, Yin, Balla, & Donaldson, 2001;
Howes et al., 2010; Powelka et al., 2004; Shi & Sottile, 2008
). Clathrin-
independent endocytosis has not been extensively studied at the growth
cone, and it may be that there are important mechanisms yet to be identified.
One form of clathrin-independent endocytosis that is involved in integrin
traffic in nonneuronal cells is the clathrin-independent carrier pathway. This
is implicated in rapid membrane turnover at the leading edge of migrating
