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remained bound to the substrate for up to an hour, failing to lengthen,
shorten, or move laterally. They continue to demonstrate organelle trans-
port; however, suggesting that fMNP/TrkB signaling also regulates adhe-
sion assembly and turnover. Concurrently, the growth cone's central
domain stopped advancing, consistent with physical restraint by the
immobilized peripheral domain that regulates movement (
Burmeister,
Rivas, & Goldberg, 1991
). Despite peripheral domain immobilization,
protrusion continued in the central domain. These results suggest
fMNP/TrkB signaling in the growth cone may mediate crosstalk between
the coordinated exo- and endocytosis of membrane, cytoskeletal dynamics,
and adhesion signaling in the peripheral but not central domain. A predic-
tion from this conclusion is that with finer control over magnetic field ap-
plication, growth cones could be steered by locally controlling exo- and
endocytosis and or locally mediating adhesion dynamics.
5. SUMMARY AND FUTURE DIRECTIONS
Signaling endosomes appear to be central players in the fundamental
organization and function of the cell as a whole, playing critical roles in neu-
ronal development and patterning, cellular maintenance, and inter- and
intracellular communication. However, our knowledge of the effects that
neurotrophin-generated signaling endosomes have on regulating growth
cone motility remains far behind our understanding of related pathways
in nonneuronal cells, and virtually nothing is known about how signaling
endosome localization and signaling works in the growth cone
in vivo
.
Compartmentalized neuronal cultures have proved to be a valuable tool
for studying and identifying some of the general mechanisms and players that
may regulate the local and retrograde actions of target-derived neuro-
trophins and the mechanisms underlying their directional trafficking in
polarized neurons. However, compartmentalized cultures do not really
recapitulate the
in vivo
environment nor are the molecules presented in
the same way as
in vivo
. To truly understand the roles singling endosome play
in physiologically relevant responses, we must develop tools for visualizing,
manipulating, and acquiring sufficient material for proteomic and genetic
analyses under
in vivo
physiologic conditions. To this end, several groups
have successfully employed selective endosomal purification-based proteo-
mic strategies coupled to mass spectrometry (
Abe et al., 2009; Pasquali,
Fialka, & Huber, 1999; Perlson et al., 2009; Stasyk et al., 2007
) or are
working to compile a complete and unbiased map of endosomal signaling
