Mechanisms of polarized membrane trafficking in neurons — Focusing in on endosomes

Abstract

Neurons are polarized cells that have a complex and unique morphology: long processes (axons and dendrites) extending far from the cell body. In addition, the somatodendritic and axonal domains are further divided into specific subdomains, such as synapses (pre- and postsynaptic specializations), proximal and distal dendrites, axon initial segments, nodes of Ranvier, and axon growth cones. The striking asymmetry and complexity of neuronal cells is necessary for their function in receiving, processing and transferring electrical signals, with each domain playing a precise function in these processes. In order to establish and maintain distinct neuronal domains, mechanisms must exist for protein delivery to specific neuronal compartments, such that each compartment has the correct functional molecular composition. How polarized membrane domains are established and maintained is a long-standing question. Transmembrane proteins, such as receptors and adhesion molecules, can be transported to their proper membrane domains by several pathways. The biosynthetic secretory system delivers newly synthesized transmembrane proteins from the ER-Golgi via the trans-Golgi network (TGN) to the plasma membrane. In addition, the endosomal system is critically involved in many instances in ensuring proper (re)targeting of membrane components because it can internalize and degrade mislocalized proteins, or recycle proteins from one domain to another. The endosomal system is thus crucial for establishing and maintaining neuronal polarity. In this review, we focus mainly on the intracellular compartments that serve as sorting stations for polarized transport, with particular emphasis on the emerging roles of endosomes.

Post-synaptic Density-95 (PSD-95) Binding Capacity of G-protein-coupled Receptor 30 (GPR30), an Estrogen Receptor That Can Be Identified in Hippocampal Dendritic Spines

“…2A, lanes 4 and 5). When full-length GPR30 was detected, a predominant band was visualized at ϳ40 -50 kDa in apparent molecular mass but also a secondary band that migrated at approximately twice the apparent molecular mass (80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(90). This secondary band potentially represents a stable, homodimeric structure for GPR30.…”

“…This atypical mechanism of receptor internalization can occur with other neuronal GPCRs located at glutamatergic synapses, including the metabotropic glutamate receptors, and it is believed to provide basal cell functions such as regulating neuronal activity and maintaining neuronal polarity (80,81). Dysregulation of such internalization mechanisms is associated with neurologic disorders including Alzheimer disease (82).…”

Rab5 and its effector FHF contribute to neuronal polarity through dynein-dependent retrieval of somatodendritic proteins from the axon

“…A fundamental but still largely unanswered question is how neurons establish and maintain this polarized distribution of proteins throughout their lifetimes. The available evidence indicates that the mechanisms of polarized sorting in neurons are quite complex (1)(2)(3). Newly synthesized transmembrane proteins travel together from their site of synthesis in the rough endoplasmic reticulum (ER) to the Golgi complex.…”

The Nodes of Ranvier: Molecular Assembly and Maintenance

“…In general, targeting proteins to specific membrane domains is achieved either by selective transport, or random transport followed by specific retention in the correct domain or removal of mislocalized proteins. Retention can be accomplished by anchoring to large molecular scaffolds or by restricting lateral diffusion (Jensen et al 2011;Lasiecka and Winckler 2011). At PNS nodes during development CAMs are clustered from a cell surface pool, whereas the accumulation of Na þ channels and ankG requires vesicular transport from the cell soma .…”