Sorting out Receptor Trafficking

in membrane or luminal/extracellular domains of these proteins, while somatodendritic signals, like basolateral signals, are found in cytoplasmic domains. However, Establishing and maintaining the proper spatial distribu-there are also contradictions to this " analogous mem-tion of integral membrane proteins is a functional neces-brane domain " hypothesis. Previous structure–function sity of all cells. This is particularly obvious in the case studies of determinants of polarized protein localization of neurons, where the polarized distribution of receptors in central neurons have been limited to nonneuronal and ion channels in a wide variety of specialized mem-proteins expressed in cultured neurons (e.g., influenza brane domains underlies the neuron's ability to receive, hemagglutinin, vesicular stomatitis virus glycoprotein) process, and transmit information. However, the identifi-or studies on individual neuronal proteins (e.g., APP, cation of determinants of neuronal polarity—the tar-transferrin receptors, synaptobrevin). In the few cases geting signals that act as molecular zip codes and the where neuronal proteins have been expressed in neu-sorting machinery that recognizes the encoded sorting rons for structure–function analyses, no general axonal signals and trafficks the proteins to their proper subcel-or somatodendritic targeting signals have emerged, per-lular destinations—remains an elusive goal. haps due to the structural variety among the examined For over 2 decades, polarized expression of mem-proteins. brane proteins has been extensively studied in kidney The current paper by Stowell and Craig (1999 [this epithelial cells, where selective localization of mem-issue of Neuron]) is a new study to analyze a family of brane proteins to either the apical or basolateral do-highly related neuronal plasma membrane proteins for mains forms the entire basis of their directional trans-targeting signals in neurons. This work focuses on meta-port. What has emerged from these studies is that a botropic glutamate receptors (mGluRs), a family of at direct pathway exists whereby the trans-Golgi network least six protein isoforms that act to couple excitatory (TGN) is able to sort membrane proteins into distinct glutamate neurotransmission and G protein–mediated trafficking vesicles capable of targeted delivery to either intracellular signaling pathways. Depending on the mGluR the apical or basolateral membrane domains (Keller and subtype, glutamate-induced G protein activation can Simons, 1997). A number of sorting signals that direct lead either to activation of phospholipase C from post-these membrane proteins to the distinct trafficking sys-synaptic sites or to inhibition of adenylyl cyclase at both tems have been identified. Apical signals are located in pre-and postsynaptic locations. The differential tar-membrane or luminal/extracellular domains, …