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Altered AMPA Receptor Trafficking and ALS
Chen Lai, Chengsong Xie, Stefanie G. McCormack, Hsueh-Cheng Chiang, Marta K. Michalak, Xian Lin, Jayanth Chandran, Hoon Shim,Mika Shimoji, Mark R. Cookson, Richard L. Huganir, Jeffrey D. Rothstein, Donald L. Price, Philip C. Wong, Lee J. Martin, J. Julius Zhu, and Huaibin Cai

Loss-of-function mutations in the ALS2 gene cause a juvenile form of amyotrophic lateral sclerosis, resulting in a progressive loss of motor neurons. This week, Lai et al., using a combination of molecular and electrophysiological approaches, found that loss of the ALS2 gene product alsin in ALS2-/- mice causes defects in AMPA receptor trafficking. When Lai et al. looked for proteins that interact with alsin, they fished out the glutamate receptor interacting protein 1 (GRIP1), whose role is to shuttle the AMPA receptor subunit GluR2 to the postsynaptic membrane. In neurons from ALS2-/- mice, neither GRIP1 nor GluR2-containing AMPA receptors made their way to the synapse. This is not inconsequential because AMPA receptors lacking GluR2 subunits are more permeable to calcium, which rendered neurons more vulnerable to excitotoxicity. Thus, impaired AMPA trafficking in the absence of normal alsin could contribute to motor neuron degeneration.
http://www.eurekalert.org/pub_releas...-ntf110206.php