Yp. Hsueh et al., DIRECT INTERACTION OF CASK LIN-2 AND SYNDECAN HEPARAN-SULFATE PROTEOGLYCAN AND THEIR OVERLAPPING DISTRIBUTION IN NEURONAL SYNAPSES/, The Journal of cell biology, 142(1), 1998, pp. 139-151
CASK, the rat homolog of a gene (LIN-2) required for vulval differenti
ation 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 consist
ent with biochemical studies showing the presence of CASK in soluble a
nd synaptosomal membrane fractions and its enrichment in postsynaptic
density fractions of rat brain. By yeast two-hybrid screening, a speci
fic interaction was identified between the PDZ domain of CASK and the
COOH terminal tail of syndecan-2, a cell surface heparan sulfate prote
oglycan (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 CAS
K, 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 syndeca
n suggests a potential role for these proteins in adhesion and signali
ng at neuronal synapses.