Gross Isabel, Brandt Nicola, Vonk Danara, Köper Franziska, Wöhlbrand Lars, Rabus Ralf, Witt Martin, Heep Axel, Plösch Torsten, Hipp Mark S, Bräuer Anja U
Research Group Anatomy, School of Medicine and Health Sciences, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany.
School of Medicine and Health Sciences, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany.
Front Cell Neurosci. 2022 Apr 15;16:797588. doi: 10.3389/fncel.2022.797588. eCollection 2022.
During adult neurogenesis, neuronal stem cells differentiate into mature neurons that are functionally integrated into the existing network. One hallmark during the late phase of this neurodifferentiation process is the formation of dendritic spines. These morphological specialized structures form the basis of most excitatory synapses in the brain, and are essential for neuronal communication. Additionally, dendritic spines are affected in neurological disorders, such as Alzheimer's disease or schizophrenia. However, the mechanisms underlying spinogenesis, as well as spine pathologies, are poorly understood. Plasticity-related Gene 5 (PRG5), a neuronal transmembrane protein, has previously been linked to spinogenesis . Here, we analyze endogenous expression of the PRG5 protein in different mouse brain areas, as well as on a subcellular level. We found that native PRG5 is expressed dendritically, and in high abundance in areas characterized by their regenerative capacity, such as the hippocampus and the olfactory bulb. During adult neurogenesis, PRG5 is specifically expressed in a late phase after neuronal cell-fate determination associated with dendritic spine formation. On a subcellular level, we found PRG5 not to be localized at the postsynaptic density, but at the base of the synapse. In addition, we showed that PRG5-induced formation of membrane protrusions is independent from neuronal activity, supporting a possible role in the morphology and stabilization of spines.
在成体神经发生过程中，神经干细胞分化为成熟神经元，并在功能上整合到现有的神经网络中。这种神经分化过程后期的一个标志是树突棘的形成。这些形态特殊的结构构成了大脑中大多数兴奋性突触的基础，对神经元通讯至关重要。此外，树突棘在神经疾病如阿尔茨海默病或精神分裂症中会受到影响。然而，关于树突棘形成以及树突棘病变的潜在机制，我们知之甚少。可塑性相关基因5（PRG5）是一种神经元跨膜蛋白，此前已被证明与树突棘形成有关。在此，我们分析了PRG5蛋白在不同小鼠脑区以及亚细胞水平上的内源性表达。我们发现，天然PRG5在树突上表达，并且在具有再生能力的区域如海马体和嗅球中大量表达。在成体神经发生过程中，PRG5在神经元细胞命运确定后与树突棘形成相关的晚期阶段特异性表达。在亚细胞水平上，我们发现PRG5并不定位于突触后致密区，而是位于突触基部。此外，我们还表明，PRG5诱导的膜突起形成与神经元活动无关，这支持了其在树突棘形态和稳定方面可能发挥的作用。
