Biology Reference
In-Depth Information
Labile
proteins
Essential
proteins
Ornithine
decarboxylase
Uch-l1
Nmnat2
App
BACE
Jnk1
Tbce
a
-synuclein
Huntingtin
Neurofilament
light chain
tau
Proteins with no
evidence for local
synthesis
Figure 5.4. Venn diagram showing examples of how axonal proteins can be categorized into
essential, labile, and not locally synthesized. For essential and nonessential proteins,
see Tables 5.1 and 5.2. The list of axonal mRNAs detected by Willis et al. (2007) is used
as a guide to locally synthesized proteins, but note that this list is growing (Gumy et al.,
2009, 2010), and validation at the protein level will be important. The full list in
mature axons in vivo could also be different. Half-life data is based on the following
references (Bennett et al., 1999; Das et al., 2007; Davis, 2000; Feuillette et al., 2005;
Gilley and Coleman, 2010; Iwami et al., 1990; Kabuta et al., 2008; Lyckman et al., 1998;
Martin et al., 2002; Millecamps et al., 2007; Tesco et al., 2007; Yuan et al., 2009). For the
purposes of this figure, “short” half-life is defined as below 24 h, as this is theoretically
too short to reach the ends of long human axons unless the protein is somehow
stabilized. However, note that axonal half-lives could sometimes be different from
those measured in cell cultures.
primary culture, is essential for their survival (Gilley and Coleman, 2010). Its
rapid turnover in axons is normally replaced by fast anterograde axonal transport
of newly synthesized protein, but if transport or synthesis of Nmnat2 fails, this
triggers Wallerian-like degeneration of the axon. An important future direction
will be to identify more such proteins, particularly by knowing more about
protein half-lives in axons. Manipulation of the expression, transport, or degra-
dation of such proteins could open new therapeutic opportunities in axonal
disorders. It would also be interesting to know whether neurons use similar
mechanisms to regulate axonal survival
in disease, after injury or during
development.
Another approach to understanding anterograde survival signals is to
study the axonal roles of proteins that mediate survival signaling in many cells.
Although mechanisms of axon degeneration and cell death differ (Deckwerth
