Pilpel Yair, Segal Menahem
Department of Neurobiology, The Weizmann Institute, Rehovot, Israel.
J Neurochem. 2006 Jun;97(5):1379-92. doi: 10.1111/j.1471-4159.2006.03825.x. Epub 2006 Apr 21.
We studied the lysophosphatidic acid receptor-1 (LPA1) gene, which we found to be expressed endogenously in cultured hippocampal neurons, and in vivo in young (1-week-old) rat brain slices. Overexpressed green fluorescent protein (GFP)-tagged, membrane-associated LPA1 accumulated in a punctate manner over the entire dendritic tree and caused an increase in dendritic spine density. About half of the dendritic spines in the LPA1-transfected neurons displayed distinct fluorescent puncta, and this subset of spines was also substantially larger than puncta-free, LPA1-transfected or control GFP spines. This phenotype could also be seen in cells transfected with a ligand-binding, defective mutant and is therefore not dependent on interaction with an ambient ligand. While spontaneous miniature excitatory synaptic currents were of the same amplitudes, they decayed slower in LPA1-transfected neurons compared with GFP controls. We propose that LPA1 may play a role in the formation and modulation of the dendritic spine synapse.
我们研究了溶血磷脂酸受体-1（LPA1）基因，发现其在培养的海马神经元中内源性表达，且在幼龄（1周龄）大鼠脑切片中也有体内表达。过表达的绿色荧光蛋白（GFP）标记的膜相关LPA1以点状方式聚集在整个树突树上，并导致树突棘密度增加。LPA1转染神经元中约一半的树突棘显示出明显的荧光点，并且这一子集的树突棘也明显大于无荧光点的LPA1转染或对照GFP树突棘。在用配体结合缺陷突变体转染的细胞中也可观察到这种表型，因此它不依赖于与周围配体的相互作用。虽然自发微小兴奋性突触电流的幅度相同，但与GFP对照相比，它们在LPA1转染神经元中的衰减更慢。我们提出，LPA1可能在树突棘突触的形成和调节中发挥作用。
