El-Husseini A E, Topinka J R, Lehrer-Graiwer J E, Firestein B L, Craven S E, Aoki C, Bredt D S
Departments of Physiology and University of California, San Francisco, California 94143, USA.
J Biol Chem. 2000 Aug 4;275(31):23904-10. doi: 10.1074/jbc.M909919199.
The postsynaptic density protein PSD-95 and related membrane-associated guanylate kinase (MAGUK) proteins assemble signal transduction complexes at sites of cell-cell contact including synapses. Whereas PSD-95 and PSD-93 occur only at postsynaptic sites in hippocampal neurons, SAP-102 also occurs in axons. In heterologous cells, PSD-95 and PSD-93 mediate cell surface ion channel clustering, but SAP-102 and SAP-97 do not. This selective ion channel clustering activity by MAGUKs is explained by differential palmitoylation, as PSD-93 and PSD-95 are palmitoylated though SAP-97, and SAP-102 are not. Rather than being palmitoylated, we find that N-terminal cysteines from SAP-102 tightly bind to zinc. And, appending the N terminus of SAP-102 to PSD-95 results in localization of the chimera to both axons and dendrites. These data suggest that lipid modifications and heavy metal associations with the N termini of MAGUKs mediate differential functions and subcellular localizations of these synaptic scaffolds.
突触后致密蛋白PSD - 95及相关膜相关鸟苷酸激酶（MAGUK）蛋白在包括突触在内的细胞间接触位点组装信号转导复合物。PSD - 95和PSD - 93仅存在于海马神经元的突触后位点，而SAP - 102也存在于轴突中。在异源细胞中，PSD - 95和PSD - 93介导细胞表面离子通道聚集，但SAP - 102和SAP - 97则不然。MAGUKs这种选择性的离子通道聚集活性可由不同的棕榈酰化来解释，因为PSD - 93和PSD - 95被棕榈酰化，而SAP - 97和SAP - 102未被棕榈酰化。我们发现，与棕榈酰化不同，SAP - 102的N端半胱氨酸紧密结合锌。并且，将SAP - 102的N端附加到PSD - 95上会导致嵌合体定位于轴突和树突。这些数据表明，MAGUKs的N端与脂质修饰和重金属的结合介导了这些突触支架的不同功能和亚细胞定位。
