Biology Reference
In-Depth Information
and Johnson, 1994; Finn
, 2000), some steps could still be shared. Exposure
of phosphatidyl serine on the external surface of degenerating axons directly
mirrors one event during apoptosis (Ivins
et al.
, 2003), and
the involvement of the apoptotic effector caspase 6 in axon death after trophic
factor deprivation also suggests similarities (Nikolaev
et al.
, 1998; Sievers
et al.
, 2009). Thus, it is
interesting that survival and stress signaling pathways involving PI3 kinases,
Erk1/2, Erk5, and Jnk all have important axonal roles, including retrograde
signaling of axonal damage, neurotrophin signaling, and regulating axonal trans-
port (Cavalli
et al.
et al.
, 2005; Chada and Hollenbeck, 2004; Horiuchi
et al.
, 2005;
Perlson
, 2001). Mek/Erk signaling and Jnk signaling
have also been reported to influence axon survival (Macinnis and Campenot,
2005; Miller
et al.
, 2005; Watson
et al.
, 2009). An important future direction will be to understand
the anterograde transport of these molecules and their regulators, and what
influence this has on axon survival.
Neurotrophins are also now known to be transported anterogradely in
axons, including Bdnf, NT-3, and Gdnf (von Bartheld
et al.
, 2001). This process
influences the functions and survival of postsynaptic cells (Caleo
et al.
et al.
, 2003;
Fawcett
et al.
, 1998), associated glia (Ng
et al.
, 2007), and the axon itself (Menna
et al.
, 2003), at least during development. Neurotrophin receptors involved in
retrograde signaling clearly also have to be delivered by anterograde axonal
transport. Thus, anterograde cargoes that may regulate axon survival include
well-studied intracellular signaling proteins and intercellular ligands and their
receptors whose delivery to axons influences cross-talk with supporting glia and
other cells.
VIII. ADHESION MOLECULES
Adhesion molecules also have roles in survival signaling in many cell types and
feature prominently in the list of proteins essential for axon survival (Table 5.1).
Without efficient anterograde transport, these will also be unable to fulfill their
important axonal roles such as contributing to axon-glial interactions. Mechan-
isms of glial support for axons, an absolute requirement for axon survival
,
have been extensively reviewed elsewhere (Nave and Trapp, 2008), so this
chapter focuses on events on the axonal side.
Axonal L1 CAM is needed to maintain, but not to establish, Schwann
cell ensheathment of unmyelinated sensory axons (Haney
in vivo
et al.
, 1999), probably
through interaction with Schwann cell
, 2005). Without
it, this axon subset is progressively lost. Interestingly, unmyelinated sympathetic
fibers are unaffected, suggesting that different mechanisms mediate this interac-
tion in different peripheral nerve axons. L1 also appears to be essential in the
optic nerve prior
1-integrins (Itoh
et al.
to myelination, with axonal ankyrin
B
probably acting
