Tsunoda S, Sun Y, Suzuki E, Zuker C
Howard Hughes Medical Institute and Departments of Biology and Neurosciences, University of California at San Diego, La Jolla, California 92093-0649, USA.
J Neurosci. 2001 Jan 1;21(1):150-8. doi: 10.1523/JNEUROSCI.21-01-00150.2001.
In Drosophila photoreceptors the multivalent PDZ protein INAD organizes the phototransduction cascade into a macromolecular signaling complex containing the effector PLC, the light-activated TRP channels, and a regulatory PKC. Previously, we showed that the subcellular localization of INAD signaling complexes is critical for signaling. Now we have examined how INAD complexes are anchored and assembled in photoreceptor cells. We find that trp mutants, or transgenic flies expressing inaD alleles that disrupt the interaction between INAD and TRP, cause the mislocalization of the entire transduction complex. The INAD-TRP interaction is not required for targeting but rather for anchoring of complexes, because INAD and TRP can be targeted independently of each other. We also show that, in addition to its scaffold role, INAD functions to preassemble transduction complexes. Preassembly of signaling complexes helps to ensure that transduction complexes with the appropriate composition end up in the proper location. This may be a general mechanism used by cells to target different signaling machinery to the pertinent subcellular location.
在果蝇光感受器中，多价PDZ蛋白INAD将光转导级联组织成一个大分子信号复合物，该复合物包含效应器磷脂酶C（PLC）、光激活的瞬时受体电位（TRP）通道和一种调节性蛋白激酶C（PKC）。此前，我们表明INAD信号复合物的亚细胞定位对信号传导至关重要。现在我们研究了INAD复合物在光感受器细胞中是如何锚定和组装的。我们发现，trp突变体或表达破坏INAD与TRP之间相互作用的inaD等位基因的转基因果蝇会导致整个转导复合物的定位错误。INAD与TRP的相互作用对于复合物的靶向并非必需，而是对于复合物的锚定是必需的，因为INAD和TRP可以彼此独立地靶向。我们还表明，除了其支架作用外，INAD还具有预组装转导复合物的功能。信号复合物的预组装有助于确保具有适当组成的转导复合物最终位于合适的位置。这可能是细胞将不同信号传导机制靶向到相关亚细胞位置所采用的一种普遍机制。
