RT Journal Article
SR Electronic
T1 PSD-93 Knock-Out Mice Reveal That Neuronal MAGUKs Are Not Required for Development or Function of Parallel Fiber Synapses in Cerebellum
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3085
OP 3091
DO 10.1523/JNEUROSCI.21-09-03085.2001
VO 21
IS 9
A1 Aaron W. McGee
A1 J. Rick Topinka
A1 Kouichi Hashimoto
A1 Ronald S. Petralia
A1 Sho Kakizawa
A1 Frederick Kauer
A1 Andrea Aguilera-Moreno
A1 Robert J. Wenthold
A1 Masanobu Kano
A1 David S. Bredt
YR 2001
UL http://www.jneurosci.org/content/21/9/3085.abstract
AB Membrane-associated guanylate kinases (MAGUKs) are abundant postsynaptic density (PSD)-95/discs large/zona occludens-1 (PDZ)-containing proteins that can assemble receptors and associated signaling enzymes at sites of cell–cell contact, including synapses. PSD-93, a postsynaptic neuronal MAGUK, has three PDZ domains that can bind to specific ion channels, including NMDA δ2 type glutamate receptors, as well as Shaker and inward rectifier type K+ channels, and can mediate clustering of these channels in heterologous cells. Genetic analyses ofDrosophila show that MAGUKs play critical roles in synaptic development because mutations of discs large disrupt the subsynaptic reticulum and block postsynaptic clustering of Shaker K+ channels. It is uncertain whether MAGUKs play an essential role in the development of central synapses. There are four neuronal MAGUKs with overlapping expression patterns in the mammalian brain; however, we find PSD-93 is the only MAGUK expressed in cerebellar Purkinje neurons. Therefore, we targeted disruption of PSD-93 in mouse. Despite the absence of MAGUK immunoreactivity in Purkinje neurons from the knock-outs, these mice have no structural or functional abnormality in cerebellum. Both the dendritic architecture and the postsynaptic localization of PSD-93 interacting proteins remain intact at light and electron microscopic levels in the knock-outs. Postsynaptic Purkinje cell responses, monosynaptic climbing fiber innervation, and cerebellar-dependent behaviors are also normal. Our data demonstrate that MAGUK proteins of the PSD-93/95 family are not essential for development of certain central synapses but may instead participate in specialized aspects of synaptic signaling and plasticity.