Srivastava Yogesh, Donta Maxsam, Mireles Lydia L, Paulucci-Holthauzen Adriana, Waxham M Neal, McCrea Pierre D
Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Program in Genetics and Epigenetics, University of Texas MD Anderson Cancer Center UT Health GSBS, Houston, TX, United States.
Front Cell Neurosci. 2024 Feb 13;18:1315941. doi: 10.3389/fncel.2024.1315941. eCollection 2024.
Neuronal connectivity is regulated during normal brain development with the arrangement of spines and synapses being dependent on the morphology of dendrites. Further, in multiple neurodevelopmental and aging disorders, disruptions of dendrite formation or shaping is associated with atypical neuronal connectivity. We showed previously that Pdlim5 binds delta-catenin and promotes dendrite branching. We report here that Pdlim5 interacts with PalmD, a protein previously suggested by others to interact with the cytoskeleton (e.g., adducin/spectrin) and to regulate membrane shaping. Functionally, the knockdown of PalmD or Pdlim5 in rat primary hippocampal neurons dramatically reduces branching and conversely, PalmD exogenous expression promotes dendrite branching as does Pdlim5. Further, we show that each proteins' effects are dependent on the presence of the other. In summary, using primary rat hippocampal neurons we reveal the contributions of a novel Pdlim5:PalmD protein complex, composed of functionally inter-dependent components responsible for shaping neuronal dendrites.
在正常脑发育过程中，神经元连接性受到调控，棘突和突触的排列依赖于树突的形态。此外，在多种神经发育和衰老疾病中，树突形成或塑形的破坏与非典型神经元连接性相关。我们之前表明，Pdlim5结合δ连环蛋白并促进树突分支。我们在此报告，Pdlim5与PalmD相互作用，PalmD是一种先前被其他人认为与细胞骨架（如内收蛋白/血影蛋白）相互作用并调节膜塑形的蛋白质。在功能上，敲低大鼠原代海马神经元中的PalmD或Pdlim5会显著减少分支，相反，PalmD的外源性表达与Pdlim5一样促进树突分支。此外，我们表明每种蛋白质的作用都依赖于另一种蛋白质的存在。总之，利用原代大鼠海马神经元，我们揭示了一种新型Pdlim5:PalmD蛋白复合物的作用，该复合物由负责塑造神经元树突的功能相互依赖的成分组成。
