Ethell I M, Yamaguchi Y
The Burnham Institute, La Jolla, California 92037, USA.
J Cell Biol. 1999 Feb 8;144(3):575-86. doi: 10.1083/jcb.144.3.575.
Dendritic spines are small protrusions that receive synapses, and changes in spine morphology are thought to be the structural basis for learning and memory. We demonstrate that the cell surface heparan sulfate proteoglycan syndecan-2 plays a critical role in spine development. Syndecan-2 is concentrated at the synapses, specifically on the dendritic spines of cultured hippocampal neurons, and its accumulation occurs concomitant with the morphological maturation of spines from long thin protrusions to stubby and headed shapes. Early introduction of syndecan-2 cDNA into immature hippocampal neurons, by transient transfection, accelerates spine formation from dendritic protrusions. Deletion of the COOH-terminal EFYA motif of syndecan-2, the binding site for PDZ domain proteins, abrogates the spine-promoting activity of syndecan-2. Syndecan-2 clustering on dendritic protrusions does not require the PDZ domain-binding motif, but another portion of the cytoplasmic domain which includes a protein kinase C phosphorylation site. Our results indicate that syndecan-2 plays a direct role in the development of postsynaptic specialization through its interactions with PDZ domain proteins.
树突棘是接受突触的小突起，并且树突棘形态的变化被认为是学习和记忆的结构基础。我们证明细胞表面硫酸乙酰肝素蛋白聚糖syndecan-2在树突棘发育中起关键作用。Syndecan-2集中在突触处，特别是在培养的海马神经元的树突棘上，并且其积累与树突棘从长而细的突起形态成熟为粗短和有头形状同时发生。通过瞬时转染将syndecan-2 cDNA早期引入未成熟的海马神经元，可加速树突突起形成树突棘。删除syndecan-2的COOH末端EFYA基序（PDZ结构域蛋白的结合位点）可消除syndecan-2的促进树突棘形成的活性。Syndecan-2在树突突起上的聚集不需要PDZ结构域结合基序，而是需要细胞质结构域的另一部分，该部分包括蛋白激酶C磷酸化位点。我们的结果表明，syndecan-2通过与PDZ结构域蛋白相互作用，在突触后特化的发育中起直接作用。
