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regions through the secretory pathway, before being internalized and
redirected through endosomes to their necessary location by transcytosis
( Lasiecka & Winckler, 2011; Winckler, 2004; Winckler & Mellman,
2010 ). These processes may be subject to further regulation as a neuron ma-
tures, stops growing, and becomes electrically active. As this occurs, the
axon initial segment (AIS) develops. This is a structure rich in ion channels
that is involved in propagating the action potential, but it is also involved in
regulating entry into the axon ( Lasiecka, Yap, Vakulenko, & Winckler,
2009; Rasband, 2010 ).
Below, we examine the mechanisms involved in regulating entry into
the axon, traffic within the axon, and traffic at the growth cone. We discuss
the literature regarding axonal trafficking of integrins and related molecules
such as the adhesion molecule L1/NgCAM, and tyrosine kinase (Trk)
receptors.
3.1. Regulated entry to the axon
In some CNS neurons, integrin distribution is limited to the somato-
dendritic domain, with a sharp cut off at the beginning of the axon (Elske
Franssen, Melissa Andrews, James Fawcett, unpublished results; Fig. 3.2 ),
but integrins are transported unimpeded into PNS sensory axons. Integrin
transport into some axons in theCNS is therefore blocked, providing one ex-
planation for their poor regenerative ability. Because of the sharp cut off of
integrins at the beginning of the axon, it is possible that axonal trafficking
of integrins is subject to regulation by the AIS. This is a complex domain that
forms
the transition between the somatodendritic and the axonal
Integrin Beta1
AnkG
Figure 3.2 b 1 integrin expression is restricted to the somatodendritic domain in some
CNS neurons in culture. The image shown is an E18 cortical neuron cultured for 14 days,
labeled for b 1 integrin (green) and the axonal initial segment marker Ankyrin G (AnkG,
red). Scale bar is 10
m.
m
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