TY - JOUR
T1 - Characterization of MALS/Velis-1, -2, and -3
T2 - A family of mammalian LIN- 7 homologs enriched at brain synapses in association with the postsynaptic density-95/NMDA receptor postsynaptic complex
AU - Jo, Kiwon
AU - Derin, Rachel
AU - Li, Min
AU - Bredt, David S.
PY - 1999/6/1
Y1 - 1999/6/1
N2 - Protein assembly at the postsynaptic density (PSD) of neuronal synapses is mediated in part by protein interactions with PSD-95/discs large/zona occludens-1 (PDZ) motifs. Here, we identify MALS-1, -2, -3, a family of small synaptic proteins containing little more than a single PDZ domain. MALS-1, - 2, and -3 are mammalian homologs LIN-7, a Caenorhabditis elegans protein essential for vulval development. In contrast to functions for LIN-7 in epithelial cells, MALS-1 and -2 are selectively expressed in specific neuronal populations in brain and are enriched in PSD fractions, in cultured hippocampal neurons, MALS proteins are clustered together with PSD-95 and NMDA type glutamate receptors, consistent with a postsynaptic localization for MALS proteins. Immunoprecipitation and affinity chromatography studies readily identify association of MALS with PSD-95 and an NMDA receptor subunit. The PDZ domain of MALS selectively binds to peptides terminating in E-T/S-R/X-V/I/L, which corresponds to the C terminus of NMDA type 2 receptors and numerous other ion channels at the PSD. This work suggests a role for MALS proteins in regulating recruitment of neurotransmitter receptors to the PSD.
AB - Protein assembly at the postsynaptic density (PSD) of neuronal synapses is mediated in part by protein interactions with PSD-95/discs large/zona occludens-1 (PDZ) motifs. Here, we identify MALS-1, -2, -3, a family of small synaptic proteins containing little more than a single PDZ domain. MALS-1, - 2, and -3 are mammalian homologs LIN-7, a Caenorhabditis elegans protein essential for vulval development. In contrast to functions for LIN-7 in epithelial cells, MALS-1 and -2 are selectively expressed in specific neuronal populations in brain and are enriched in PSD fractions, in cultured hippocampal neurons, MALS proteins are clustered together with PSD-95 and NMDA type glutamate receptors, consistent with a postsynaptic localization for MALS proteins. Immunoprecipitation and affinity chromatography studies readily identify association of MALS with PSD-95 and an NMDA receptor subunit. The PDZ domain of MALS selectively binds to peptides terminating in E-T/S-R/X-V/I/L, which corresponds to the C terminus of NMDA type 2 receptors and numerous other ion channels at the PSD. This work suggests a role for MALS proteins in regulating recruitment of neurotransmitter receptors to the PSD.
KW - C. elegans
KW - LIN-7
KW - MALS
KW - NMDA receptor
KW - PDZ
KW - PSD-95
KW - Postsynaptic density
UR - http://www.scopus.com/inward/record.url?scp=0033151584&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033151584&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.19-11-04189.1999
DO - 10.1523/jneurosci.19-11-04189.1999
M3 - Article
C2 - 10341223
AN - SCOPUS:0033151584
SN - 0270-6474
VL - 19
SP - 4189
EP - 4199
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 11
ER -