Biology Reference
In-Depth Information
signaling endosome localization in neuronal growth cones support these views
and place the neurotrophin signaling endosome in a central role regulating growth
cone motility during axon growth and regeneration.
1. INTRODUCTION
The nervous systempatterns itself with remarkable precision due to the
path-finding abilities of the motile tip of growing neurites, the growth cone.
Growth cones direct neurite growth by altering their motility in response to
extracellular cues including neurotrophins (Nt). Neurotrophin-activated
signaling endosomes
transmit long-distance, regulatory signals between nerve
terminals and the soma to regulate developmental patterning and survival.
However, neurotrophin signaling can also act locally at the growth cone
to affect neurite growth rate and guidance during development and
regeneration.
How do neurotrophin signaling endosomes locally regulate growth cone
motility? Current data on signaling endosome biology are expanding our
views on signaling endosomes from long-distance, target-derived, retrograde
messengers to also include locally acting signaling complexes whose spatio-
temporal localization directs membrane trafficking, receptor localization and
activity, cell adhesion molecule (CAM) distribution, compartmentalized
signaling, cytoskeletal effector localization, and local translation of new
proteins intra-axonally and in the growth cone. These emerging views place
the signaling endosome in a central role in organizing and compartmental-
izing numerous signaling pathways regulating growth cone motility. Recent
nanoparticle-mediated approaches applied to manually manipulate signaling
endosomes within the growth cone support these views by showing that
signaling endosome
localization
regulates membrane, cytoskeletal, and
adhesion-mediated processes underlying growth cone motility.
1.1. The growth cone's vesicular matrix
Growth cone motility is driven by a complex, exquisitely controlled exo-
and endocytic vesicular matrix that underlies the activities of three distinct,
interrelated events necessary to elongate and steer neurites: protrusion,
engorgement, and consolidation (
Goldberg & Burmeister, 1986
). Each
of these events requires the polarized delivery of vesicles carrying lipid
and protein cargoes necessary to selectively assemble, disassemble, and
