%0 Journal Article
%T Ubiquitination of Neurotransmitter Receptors and Postsynaptic Scaffolding Proteins
%A Amy W. Lin
%A Heng-Ye Man
%J Neural Plasticity
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/432057
%X The human brain is made up of an extensive network of neurons that communicate by forming specialized connections called synapses. The amount, location, and dynamic turnover of synaptic proteins, including neurotransmitter receptors and synaptic scaffolding molecules, are under complex regulation and play a crucial role in synaptic connectivity and plasticity, as well as in higher brain functions. An increasing number of studies have established ubiquitination and proteasome-mediated degradation as universal mechanisms in the control of synaptic protein homeostasis. In this paper, we focus on the role of the ubiquitin-proteasome system (UPS) in the turnover of major neurotransmitter receptors, including glutamatergic and nonglutamatergic receptors, as well as postsynaptic receptor-interacting proteins. 1. Introduction Neurons are highly complex cells that form a network of connectivity throughout the brain via specialized structures called synapses. The human brain contains approximately 85¨C100 billion neurons that can generate an estimated 100 trillion synapses [1]. These synapses maintain a careful balance between network plasticity and stability through finely controlled mechanisms such as intracellular trafficking and posttranslational modification of synaptic proteins. One such modification is ubiquitination, which is known to play a role in synaptic physiology and synapse formation, as well as in synaptic protein trafficking, stability, internalization, and degradation [2]. Malfunction of the ubiquitin system is also involved in the development of brain disorders such as autism, Alzheimer¡¯s disease, Huntington¡¯s disease, amyotrophic lateral sclerosis (ALS), and Parkinson¡¯s disease [3]. Ubiquitin (Ub) is a small, highly conserved protein expressed in all eukaryotic cells that modulates an extensive range of biological functions including DNA repair, transcription, endocytosis, autophagy, and protein degradation. Structurally, ubiquitin is an 8.5£¿kDa, 76 amino acid polypeptide that forms a compact structure with an exposed carboxy terminal tail containing a diglycine motif that can be covalently ligated via an isopeptide bond to the primary ¦Å-amino group of lysine (Lys) residues on a target substrate. This occurs through an enzymatic process termed ubiquitination, a reversible posttranslational modification that can affect the structure and activity of the targeted protein, along with its localization and binding interaction to other partners. The first step of this pathway involves the biochemical priming of ubiquitin by the E1 ubiquitin-activating
%U http://www.hindawi.com/journals/np/2013/432057/