Biology Reference
In-Depth Information
Gundersen, 2005
), while intracellular transport coupled with recycling is
important for the redistribution of integrins to new adhesion sites (
Jovic,
Naslavsky, Rapaport, Horowitz, & Caplan, 2007; Roberts, Barry,
Woods, van der Sluijs, & Norman, 2001; Woods, White, Caswell, &
Norman, 2004
), and it is becoming apparent that these processes are impor-
tant for steering the growth cone during axon growth (
Hines et al., 2010;
Tojima et al., 2007; Tojima, Itofusa, & Kamiguchi, 2010
).
Integrins are therefore subject to intricate regulation and are part of a large
complex of proteins that function to regulate the cytoskeleton and intracel-
lular signaling pathways to control cellmigration events. Can integrins bema-
nipulated to increase axonal regeneration after injury in the adult CNS? In this
review, we focus on the intrinsicmechanisms that regulate axon regeneration
after injury and address the extent to which integrins are involved. As correct
localization is paramount to integrin function, we further focus on the
intrinsic mechanisms involved in regulating integrin traffic, and discuss the
regulation of traffic in the axon and at the growth cone.
2. INTEGRINS AND INTRINSIC MECHANISMS OF AXON
REGENERATION
There has been some success from strategies aimed at counteracting
the environmental inhibition within the lesion core and surrounding milieu,
however, injured neurons in the adult CNS remain reluctant to extend
axons. Research into intrinsically stimulating regenerative growth state
appears crucial for achieving long-distance regrowth.
2.1. Conditioning lesions and cAMP
Nearly 30 years ago,
Richardson and Issa (1984)
discovered that a peripheral
conditioning lesion of the sciatic nerve (crushing or cutting of the peripheral
branch of the dorsal root ganglion, DRG) induced a robust growth response
in the central branch of the DRG, resulting in damaged fibers growing into a
peripheral nerve graft implanted into the spinal cord. It was subsequently
discovered that injured dorsal column axons could be further stimulated
by inducing the peripheral lesion 1 week prior to the central lesion
(
Neumann &Woolf, 1999
). This is because DRG neurons possess an intrin-
sic ability to regenerate their axons, which can be stimulated by a condition-
ing lesion to generate an enhanced intrinsic growth response. Studies into
the mechanism behind this increase in intrinsic growth potential have shown
