Biology Reference
In-Depth Information
A
Central branch
(i) Uninjured
Peripheral branch
DRG
(ii) Preconditioning periheral lesion
Cell body response:
cAMP, altered transcription
(iii) Central lesion following
preconditioning peripheral lesion
Regeneration
Integrin expression
Peripheral lesion
Central lesion
B
integrins
Rab11 domain
ARF6 domain
Rab11
ARF6
slow
slow
Rab11
Rab11
Rab11
ARF6
ARF6
transcytosis
ARF6
fast
fast
ARF6
Rab11
Rab11
ARF6
ARF6 GTP favors integrin endocytosis and retrograde transport
ARF6 GDP favors integrin recycling and anterograde transport
Figure 3.1 Schematic diagrams of a DRG neuron response to a preconditioning lesion
of the peripheral branch, and endocytic transport mechanisms of integrins into DRG
axons. A preconditioning peripheral lesion results in a cell body response, including
elevated cAMP and altered gene transcription (
Qiu et al., 2002
). A subsequent lesion
of the central branch then causes increased axonal expression of integrins, with an
accompanying increase in axon regeneration (
Gardiner et al., 2007
). This does not happen
without the preconditioning lesion (A). Integrins traffic into DRG axons via transcytosis
mediated by the recycling endosome GTPases Rab11 and ARF6. Rab11 mediates slow
transport of integrins in an oscillatory fashion, while ARF6 mediates fast directional
transport (B). Growth cone integrins are subject to internalization, redirection, and
recycling also mediated by Rab11 and ARF6 (
Eva et al., 2010, 2012
).
