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Binding of MAGUK family proteins to Neuroligin 1


Hope Kean Photo

Winston Churchill High School (Maryland)

Abstract

Neuroligins (NLs) are cell adhesion molecules (CAMs) that play a vital role in post-synaptic organization.  Their intracellular tails contain a principal binding site on their cytoplasmic tails (C-tails), the postsynaptic density protein-95/disks large/zonula occludens-1 (PDZ) ligand, which has been shown to bind with the PDZ domains of membrane-associated guanylate kinase (MAGUK) family proteins.  It has recently been shown that, far from straightforward linkage proteins, NLs regulate a wide variety of neuronal processes.  A major feature of NLs that allows for versatility is the PDZ binding domain. MAGUKs bind with NL at the PDZ domain and create complex networks of scaffolding proteins within the post synaptic neuron, that determine the organization of receptors as well as other structures in the postsynaptic membrane.  However, NL-1 that has its PDZ ligand truncated still displays postsynaptic potentiation of excitatory neurotransmission (Shipman, et al., 2011).  NL-1 is specific to excitatory synapses, whereas NL-2 is localized in inhibitory synapses.  Notably, the NL-1 and -2 PDZ ligands are identical.  We hypothesized that additional binding motifs are present in NL-1 or -2 that give specificity to MAGUK interactions and targeting.  We found that NL-1 C-tail lacking its PDZ ligand, NL-1 ∆PDZ, binds to PSD-95 and SAP102.  This indicates that another non-PDZ binding motif exists upstream on the C-tail.

Last updated November 27, 2013