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News tips from the Journal of Neuroscience

1. Homer is a Foursome

Mariko Kato Hayashi, Heather M. Ames, and Yasunori Hayashi

The long forms of the scaffolding protein, Homer, use their N-terminal EVH1 domain to interact with postsynaptic proteins such as metabotropic glutamate receptors (mGluRs), IP3 receptors and TRPC channels. The C-terminal coil-coiled domain allows oligomerization of Homer monomers. The short form, Homer1a, lacks the coiled-coil domains. This week, Hayashi et al. report that the long form, Homer1b, forms tetramers with all subunits arranged in parallel. The authors used a series of biophysical and imaging measures to investigate oligomerization. The linear tetramer makes it possible for Homer to act as a hub that can bring together different ligands to form signal transduction complexes. This arrangement is consistent with the known actions of Homer, for example, in linking mGluR1/5 to a downstream effector, the IP3 receptor. The Homer tetramer also interacts with another scaffolding protein, Shank. Shank forms antiparallel homodimers, thus HomerShank complexes could potentially form large three-dimensional lattices.

2. NAD to the Rescue

Yo Sasaki, Toshiyuki Araki, and Jeffrey Milbrandt

This week, Sasaki et al. tested the role of nicotinamide adenine dinucleotide (NAD) in protecting neurons from axonal degeneration. NAD acts as a cofactor for most dehydrogenases and is involved in aerobic and anaerobic ATP generation. Previous studies have indicated that overexpression of nicotinamide mononucleotide adenylyltransferase1 (Nmnat1) can protect cultured dorsal root ganglion neurons from mechanical- or neurotoxin-induced axonal degeneration. The authors tested each step in the biosynthetic pathways that can generate NAD. They expressed the biosynthetic enzymes using lentiviral constructs in DRG neurons, then assayed their effects on axonal degeneration 2472 h following axotomy. Nmnat1 had the strongest protective effect. Howev
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Contact: Sara Harris
sharris@sfn.org
202-962-4000
Society for Neuroscience
15-Aug-2006


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