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there is little evidence to suggest that integrin molecules are present in adult
CNS axons, and we find that exogenously expressed integrins are not trans-
ported into adult corticospinal axons
in vivo
(Andrews et al., unpublished
findings). There is some form of anterograde axonal transport after adult
CNS axotomy, because vesicles accumulate in retraction bulbs (
Erturk,
Hellal, Enes, & Bradke, 2007
), and axonal transport of membrane vesicles
is important because interfering with postgolgi trafficking inhibits axon ex-
tension (
Futerman & Banker, 1996; Prager-Khoutorsky & Spira, 2009
).
However, the transport mechanisms present in adult CNS axons do not
appear to allow for efficient delivery of integrins from the brain into spinal
cord axons. This may reflect a difference in transport mechanisms between
regenerative and nonregenerative axons because regenerative PNS axons
transport integrins efficiently. However, this transport limitation is restricted
to axons because there is evidence that integrins are present within dendrites
in the adult CNS (
Cingolani et al., 2008; Pozo et al., 2012; Warren et al.,
2012
). It is therefore important to understand the trafficking and transport
mechanisms that are involved in targeting integrins and related membrane
proteins into the axon.
Integrins are integral membrane proteins, and as such are translated into
the ER membrane, and subsequently reside within membranes for the du-
ration of their existence. After synthesis, membrane proteins are exported
from the ER to the Golgi in transport vesicles, and subsequently transported
via the trans-Golgi network to the surface membrane, a pathway known as
the standard secretory pathway. Once at the surface, membrane proteins can
be internalized by endocytosis, and directed via recycling endosomes back to
the cell surface, or targeted to lysosomes for degradation (
Anitei & Hoflack,
2012; Gerdes, 2008; Pfeffer, 2007; Pryor & Luzio, 2009; Stenmark, 2009
).
While in recycling endosomes, it is possible to traffic via a short loop back to
the surface membrane in the immediate vicinity or to be rerouted to a dif-
ferent part of the cell by long-loop recycling (
Caswell & Norman, 2006
).
It has therefore been proposed that there are three pathways available for
membrane proteins to reach the axon. First, they could be delivered to
the axon directly through the secretory pathway, being sorted by mecha-
nisms which target proteins immediately to their final destination (direct po-
larized delivery). Second, membrane proteins could be delivered through
the secretory pathway in a nonspecific fashion to axons, dendrites and the
cell body, and then selectively endocytosed and targeted away from regions
where they are not required, or only anchored in the regions where they are
needed (selective retention). Third, they could be targeted to specific
