Biology Reference
In-Depth Information
disassembly, and signaling (
Kolodkin & Tessier-Lavigne, 2011; Myers,
Santiago-Medina, & Gomez, 2011
). How is this “vesicular matrix”
regulated? As discussed below, “signaling endosomes” generated at the
growth cone harboring unique signaling complexes appear to play a
central role in mediating vesicular trafficking by providing mobile
platforms that organize signaling complexes into microsignaling domains
locally regulating the spatiotemporal organization of
lipid and protein
trafficking.
1.2. The signaling endosome hypothesis
Neurotrophin-generated signaling endosomes are best characterized as long-
distance, target-derived communication links. The classical signaling endo-
somes hypothesis is well reviewed (
Campenot & MacInnis, 2004; Cosker,
Courchesne, & Segal, 2008; Howe & Mobley, 2004
). Briefly, the
neurotrophins brain-derived neurotrophic factor (BDNF), nerve growth
factor (NGF), and neurotrophins-3 and -4 (NT-3, NT-4) are a family of
closely related target-derived proteins that activate distinct tropomyosin-
related kinase (Trk) receptors (
Cosker et al., 2008; Rajagopala et al., 2007
).
NGF predominantly binds to TrkA, BDNF and NT-4 to TrkB, and NT-3
to TrkC (
Campenot & MacInnis, 2004; Chao, 2003
). Each neurotrophin
also activates the p75 neurotrophin receptor with lower affinity (
Chao,
2003
). The signaling endosome hypothesis postulates that neurotrophin-Trk
receptor complexes are endocytosed at nerve terminals into signaling
endosomes that undergo dynein- and dynactin-mediated retrograde
(
Wu, Cui, He, Chen, & Mobley, 2009
) and kinesin-mediated anterograde
(
Butowt & von Bartheld, 2007, 2009; Huang, Duan, Sun, et al., 2011
)
transport in axons and in dendrites (
Sann et al., 2009; Watson et al., 2001
).
Through this transport, they signal persistently and can thereby promote
survival, and regulate neuronal development and synaptic plasticity
(
Carvalho, Caldeira, Santos, & Duarte, 2008; Sharma et al., 2010
). In the
soma, signaling endosomes influence gene expression by activating
transcription factors, including cAMP response element-binding protein
(CREB) (
Huang & Reichardt, 2003
) and E26-like transcription factors
(
Campenot & MacInnis, 2004; Ginty & Segal, 2002; Glebova & Ginty,
2005; Howe, Valletta, Rusnak, & Mobley, 2001
). In turn, both endosome
and non-endosome-based signals are anterogradely transported back to the
nerve terminal (
Cosker et al., 2008; Fainzilber, Budnik, Segal, & Kreutz,
2011
). This bidirectional communication link between nerve terminals
and soma is critical in both the central and peripheral nervous systems
