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Review
. 2012 May 10;74(3):440-51.
doi: 10.1016/j.neuron.2012.04.015.

Harnessing the power of the endosome to regulate neural development

Chan Choo Yap  1 , Bettina Winckler
Affiliations
Review

Harnessing the power of the endosome to regulate neural development

Chan Choo Yap et al. Neuron. .

Abstract

Endocytosis and endosomal trafficking play a multitude of roles in cellular function beyond regulating entry of essential nutrients. In this review, we discuss the cell biological principles of endosomal trafficking, the neuronal adaptations to endosomal organization, and the role of endosomal trafficking in neural development. In particular, we consider how cell fate decisions, polarity, migration, and axon outgrowth and guidance are influenced by five endosomal tricks: dynamic modulation of receptor levels by endocytosis and recycling, cargo-specific responses via cargo-specific endocytic regulators, cell-type-specific endocytic regulation, ligand-specific endocytic regulation, and endosomal regulation of ligand processing and trafficking.

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Figures

Figure 1
Figure 1. Membrane traffic in non-polarized cells
Eukaryotic cells contain a large number of endomembrane compartments, dedicated to biosynthetic transport of molecules to the surface as well as internalization from the surface. These compartments are dynamically interconnected via vesicular carriers and/or via maturation of earlier into later compartments. Compartment identity is ensured by distinct lipid composition and regulatory proteins. The phosphoinositides enriched on each compartment as well as the most commonly used protein markers for Golgi, trans-Golgi network (TGN), early endosomes (EE), recycling endosomes (RE), late endosomes (LE), and lysosomes (lys) are indicated. Arrows denote some of the well-studied transport steps between compartments. Not shown: Rab8, Rab13, and Rab10 are protein markers for the TGN.
Figure 2
Figure 2. Tricks of the endosome
After ligands bind to their receptors, they initiate signaling at the PM. Frequently, receptors can be endocytosed. Once endocytosed, they can either traffic to lysosomes for degradation and signal termination, or recycle in a temporally and spatially controlled fashion back to the PM. Recycling can restore responsiveness to an extracellular cue and/or deliver a ligand or signal to a different membrane domain. Endocytosed receptors can also generate various signaling endosomes where they encounter signaling components. Depending on the particular signaling endosome and the components recruited to it or present there, distinct signaling cascades can be initiated by receptors at endosomes.
Figure 3
Figure 3. Polarized endosomes in neurons
The large size and spatial heterogeneity of neurons necessitates a far-flung endosomal system that differs in many aspects from non-polarized cells. Somatic, dendritic, axonal, spine (not depicted) and synaptic (not depicted) endosomes have common and distinct regulators associated and show distinct motility profiles. In addition to local recycling, endosomes in axons and dendrites also undergo long-range anterograde and retrograde motility. Compartment maturation also occurs as endosomes travel retrogradely in axons and acidify.
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