Kayadjanian N, Lee H S, Piña-Crespo J, Heinemann S F
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, PO Box 85800, La Jolla, CA 92186-5800, USA.
Mol Cell Neurosci. 2007 Feb;34(2):219-30. doi: 10.1016/j.mcn.2006.11.001. Epub 2006 Dec 15.
Correct glutamate receptor localization in neurons is crucial for neurotransmission in the brain. Here we investigated the mechanisms underlying localization of kainate GluR5 receptors to dendrites in cultured hippocampal neurons. We find that the GluR5 distribution depends on association with GluR6 and KA2 subunits. The GluR5 subunit was expressed in distal dendrites only when GluR6 and KA2 subunits were present, whereas it was restricted to proximal dendrites in the absence of these subunits. The overlap between GluR5 distribution and the organization of microtubules in dendrites led us to examine whether KIF17, a microtubule motor protein expressed in distal dendrites, is involved in GluR5 localization to distal dendrites. We show here, for the first time that the microtubule motor protein KIF17 interacts with GluR6 and KA2 subunits and is required for GluR5 localization to distal dendrites, defining a novel mechanism that controls receptor localization in neurons.
谷氨酸受体在神经元中的正确定位对于大脑中的神经传递至关重要。在此,我们研究了在培养的海马神经元中,红藻氨酸盐型GluR5受体定位于树突的潜在机制。我们发现,GluR5的分布取决于与GluR6和KA2亚基的结合。只有当GluR6和KA2亚基存在时,GluR5亚基才会在远端树突中表达,而在没有这些亚基时,它则局限于近端树突。GluR5分布与树突中微管组织之间的重叠使我们去研究KIF17(一种在远端树突中表达的微管运动蛋白)是否参与GluR5向远端树突的定位。我们在此首次表明,微管运动蛋白KIF17与GluR6和KA2亚基相互作用,并且是GluR5定位于远端树突所必需的,这确定了一种控制神经元中受体定位的新机制。