Wente Wolf, Stroh Thomas, Beaudet Alain, Richter Dietmar, Kreienkamp Hans-Jürgen
Institut für Zellbiochemie und klinische Neurobiologie and Institut für Humangenetik, Universitätskrankenhaus Hamburg-Eppendorf, Germany.
J Biol Chem. 2005 Sep 16;280(37):32419-25. doi: 10.1074/jbc.M507198200. Epub 2005 Jul 12.
By yeast two-hybrid screening we have identified interaction partners for the intracellular C-terminal tail of the human and rodent somatostatin receptor subtype 5 (SSTR5). Interactions with the PDZ domain-containing proteins PIST and PDZK1 are mediated by the PDZ ligand motif at the C terminus of the receptor; in case of the human and mouse (but not the rat) receptors, a slight sequence variation of this motif also allows for binding of the peroxisomal receptor PEX5. PIST is Golgi-associated and retains SSTR5 in the Golgi apparatus when coexpressed with the receptor; PDZK1 on the other hand associates with the SSTR5 at the plasma membrane. Endogenous SSTR5 in the neuroendocrine AtT-20 tumor cell line is colocalized with PIST in the Golgi apparatus. On a functional level, removal of the PDZ ligand motif of the receptor does not interfere with agonist-dependent internalization of the receptor or its targeting to a Golgi-associated compartment; however, recycling of the receptor to the plasma membrane after washout of the agonist is inhibited, suggesting that the PDZ-mediated interaction of SSTR5 is required for postendocytic sorting.
通过酵母双杂交筛选，我们鉴定出了人类和啮齿动物生长抑素受体亚型5（SSTR5）细胞内C末端尾巴的相互作用伙伴。与含PDZ结构域的蛋白质PIST和PDZK1的相互作用是由受体C末端的PDZ配体基序介导的；对于人类和小鼠（但不是大鼠）受体，该基序的轻微序列变异也允许过氧化物酶体受体PEX5的结合。PIST与高尔基体相关，当与受体共表达时，它会将SSTR5保留在高尔基体中；另一方面，PDZK1在质膜处与SSTR5结合。神经内分泌AtT - 20肿瘤细胞系中的内源性SSTR5与PIST在高尔基体中共定位。在功能水平上，去除受体的PDZ配体基序不会干扰受体的激动剂依赖性内化或其靶向高尔基体相关区室；然而，激动剂洗脱后受体再循环到质膜的过程受到抑制，这表明SSTR5的PDZ介导的相互作用是内吞后分选所必需的。
