Direct interaction of CASK/LIN-2 and syndecan heparan sulfate proteoglycan and their overlapping distribution in neuronal synapses.
CASK, the rat homolog of a gene (LIN-2) required for vulval differentiation in Caenorhabditis elegans, is expressed in mammalian brain, but its function in neurons is unknown. CASK is distributed in a punctate somatodendritic pattern in neurons. By immunogold EM, CASK protein is concentrated in synapses, but is also present at nonsynaptic membranes and in intracellular compartments. This immunolocalization is consistent with biochemical studies showing the presence of CASK in soluble and synaptosomal membrane fractions and its enrichment in postsynaptic density fractions of rat brain. By yeast two-hybrid screening, a specific interaction was identified between the PDZ domain of CASK and the COOH terminal tail of syndecan-2, a cell surface heparan sulfate proteoglycan (HSPG). The interaction was confirmed by coimmunoprecipitation from heterologous cells. In brain, syndecan-2 localizes specifically at synaptic junctions where it shows overlapping distribution with CASK, consistent with an interaction between these proteins in synapses. Cell surface HSPGs can bind to extracellular matrix proteins, and are required for the action of various heparin-binding polypeptide growth/differentiation factors. The synaptic localization of CASK and syndecan suggests a potential role for these proteins in adhesion and signaling at neuronal synapses.
Hsueh
Y P
YP
Howard Hughes Medical Institute and Department of Neurobiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Yang
F C
FC
Kharazia
V
V
Naisbitt
S
S
Cohen
A R
AR
Weinberg
R J
RJ
Sheng
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019084:Fluorescent Antibody Technique, Indirect; D051528:Guanylate Kinases; D015801:Helminth Proteins; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D009703:Nucleoside-Phosphate Kinase / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D013347:Subcellular Fractions; D013569:Synapses / Q000378:metabolism*; D053669:Syndecan-2
D015801:Helminth Proteins; D019812:Heparan Sulfate Proteoglycans; C097978:Lin-2 protein, C elegans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011509:Proteoglycans; C508247:Sdc2 protein, rat; D053669:Syndecan-2; C106868:CASK kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases