Biology Reference
In-Depth Information
Like any mixture of proteins, axonal proteins have a large range of half-
lives. At one extreme, the light neurofilament protein has a half-life estimated at
3 weeks to 2.5 months, depending on the experimental system (Millecamps
et al.
,
2007; Yuan
, 2009). In contrast, App and Aplp2 have half-lives of around
4 h after being transported through the hamster optic nerve to the superior
colliculus (Lyckman
et al.
, 1998). Some axonal proteins are even less stable.
Ornithine decarboxylase has a half-life of only 5-30 min in many mammalian
tissues, although its axonal half-life has not been reported (Iwami
et al.
, 1990).
It is hard to reconcile some of these half-lives with the time taken for
proteins to reach axon termini. In the longest human axons, the most rapidly
transported cargoes take around 2 days to reach the distal ends. Thus, a half-life
of 4 h may suffice for App to reach the terminals of 1-cm hamster optic nerve
axons, but little or none should reach neuromuscular junctions in our toes, and
the viability of long blue whale axons starts to appear really questionable. For
ornithine decarboxylase, a notoriously unstable protein, the problem is even
greater, and yet it is abundant in motor axons and their terminals (Junttila
et al.
,
1993). Axonal protein synthesis could be one explanation for a subset of axonal
proteins (see below). Another intriguing prospect is that cargoes are somehow
“privileged” while they are being transported, so that the ubiquitin proteasome
system does not “see” them. Once released from the transport machinery, their
half-life could suddenly shorten.
In summary, diverse axonal proteins have half-lives ranging from
months down to hours or even minutes. Mechanisms to understand how the
more labile proteins reach the distal ends of longer axons require further investi-
gation. However, most labile proteins are likely to be depleted quickly when
transport fails, and distal regions are likely to suffer the greatest decline.
et al.
VI. AXONAL PROTEIN SYNTHESIS
After many years of controversy, it is now generally accepted that some axonal
proteins can be translated locally using axonally targeted mRNAs (Giuditta
et al.
, 2009). This seems to concern only a subset of axonal
proteins, and how much of these proteins is synthesized in axons remains unclear.
However, there is a clear capacity to synthesize some proteins locally using a
system that can respond to local events such as axonal damage (Gumy
, 2002; Gumy
et al.
et al.
,
2009; Perlson
, 2007).
Axonal protein synthesis may partially answer how labile proteins are
supplied to distal axons. For example, ornithine decarboxylase mRNA is present
in axons, at least after a conditioning lesion (Willis
et al.
, 2005) and extracellular stimuli (Willis
et al.
, 2007). Thus, the
paradox that a large amount of this very labile protein exists in distal axons
(above) could be explained if most of the protein derives from local synthesis.
et al.
