Signaling Endosomes and Growth Cone Motility in Axon Regeneration - International Review of Neurobiology - page 34

CHAPTER TWO

Signaling Endosomes and
Growth Cone Motility in Axon
Regeneration

, † ,1
* Bascom Palmer Eye Institute, University of Miami, Miami, Florida, USA
†

, † , Jeffrey L. Goldberg *

Michael B. Steketee *

Interdisciplinary Stem Cell Institute, University of Miami, Miami, Florida, USA
1 Corresponding author: e-mail address: [e-mail]

Contents
1. Introduction 36

1.1 The growth cone's vesicular matrix 36

1.2 The signaling endosome hypothesis 41

2. Signaling Endosome Formation 42

2.1 Receptor-mediated endocytosis 42

2.2 Sorting and signaling 43

2.3 Lipids and signaling 48

2.4 Signaling endosomes and intra-axonal translation 52

3. Signaling Endosome Signaling in the Growth Cone 53

3.1 Exo- and endocytosis 53

3.2 Cytoskeletal effector localization 55

3.3 Adhesion formation, signaling, and turnover 57

4. Nanoparticle-Mediated Signaling Endosome Manipulation 58

4.1 Methodology and characterization 58

4.2 Nanoparticle-mediated changes in transport 59

4.3 Altering signaling endosome localization with nanoparticles alters growth
cone motility 60

5. Summary and Future Directions 62

Acknowledgments 63

References 63

Abstract
During development and regeneration, growth cones guide neurites to their targets by
altering their motility in response to extracellular guidance cues. One class of cues critical
to nervous system development is the neurotrophins. Neurotrophin binding to their
cognate receptors stimulates their endocytosis into signaling endosomes. Current data
indicate that the spatiotemporal localization of signaling endosomes can direct diverse
processes regulating cell motility, including membrane trafficking, cytoskeletal remo-
deling, adhesion dynamics, and local translation. Recent experiments manipulating