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In-Depth Information
2.5.2 Trafficking with Cdk5
Although the precise roles of membrane trafficking events underlying axon
growth and regeneration are still under investigation, insertion of newmem-
brane and cell surface molecules, as well as retrieval and reconstruction of
plasma membrane, is indeed regulated by the common mechanisms that me-
diate neurotransmitter release and synaptic vesicle recycling. For example,
while membrane addition and axon growth requires soluble NSF-
Attachment protein Receptor (SNARE)-mediated exocytosis, membrane
retrieval and remodeling needs clathrin-mediated endocytosis (
Bloom &
Morgan, 2011
).
Research over the past decade on Cdk5 has provided informative results
on its pivotal roles in neurotransmission through phosphorylation of a myr-
iad of presynaptic substrates. In exocytosis, Cdk5 plays opposite roles in
trafficking and release of neurotransmitters. In particular, Cdk5 phosphor-
ylates synapsin to facilitate vesicle trafficking from the resting pool to the
releasable pool (
Jovanovic et al., 2001
). However, phosphorylation of
P/Q subtype voltage-gated calcium channel and Pctaire1 in the presynaptic
terminal hinders exocytosis and neurotransmitter release (
Liu, Cheng,
Gong, Fu, & Ip, 2006; Yan, Chi, Bibb, Ryan, & Greengard, 2002
). In
addition to the regulation of exocytosis, Cdk5 has been identified as a
kinase to phosphorylate at least three regulatory proteins, including
dynamin 1, amphiphysin 1, and synaptojanin 1, which are essential for
clathrin-mediated endocytosis (
Cheung, Fu, & Ip, 2006
). Although the
indispensable roles of Cdk5 in presynaptic exocytosis and endocytosis are
well accepted, the precise function of Cdk5-mediated phosphorylation
events underlying membrane trafficking during axon growth and
regeneration are largely unknown.
3. CONCLUDING REMARKS AND FUTURE PERSPECTIVES
Although the involvement of Cdk5 in developmental axon growth
and patterning is evident based on numerous
in vitro
and
in vivo
animal
models, whether Cdk5 is directly linked to regenerative axon growth
remains elusive. Indeed, an initial study demonstrated the involvement of
injury-triggered Cdk5 activation in PNS axon regeneration after facial nerve
crush (
Namgung et al., 2004
). However, due to the limited axon regener-
ation of mammalian CNS neurons, there is a lack of direct evidence to dem-
onstrate the Cdk5 function in axon regeneration in mammalian CNS. It will
