Research Group Anatomy, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, Oldenburg, Germany.
Institute of Anatomy, University Medical Center Rostock, Rostock, Germany.
Dev Dyn. 2022 Apr;251(4):714-728. doi: 10.1002/dvdy.428. Epub 2021 Oct 16.
Plasticity-related genes (Prgs/PRGs) or lipid phosphate phosphatase-related proteins (LPPRs) comprise five known members, which have been linked to neuronal differentiation processes, such as neurite outgrowth, axonal branching, or dendritic spine formation. PRGs are highly brain-specific and belong to the lipid phosphate phosphatases (LPPs) superfamily, which influence lipid metabolism by dephosphorylation of bioactive lipids. PRGs, however, do not possess enzymatic activity, but modify lipid metabolism in a way that is still under investigation.
We analyzed mRNA expression levels of all Prgs during mouse brain development, in the hippocampus, neocortex, olfactory bulbs, and cerebellum. We found different spatio-temporal expression patterns for each of the Prgs, and identified a high expression of the uncharacterized Prg4 throughout brain development. Unlike its close family members PRG3 and PRG5, PRG4 did not induce filopodial outgrowth in non-neuronal cell lines, and does not localize to the plasma membrane of filopodia.
We showed PRG4 to be highly expressed in the developing and the adult brain, suggesting that it is of vital importance for normal brain function. Despite its similarities to other family members, it seems not to be involved in changes of cell morphology; instead, it is more likely to be associated with intracellular signaling.
可塑性相关基因(Prgs/PRGs)或类脂磷酸磷酸酶相关蛋白(LPPRs)包含五个已知成员,它们与神经元分化过程有关,如轴突生长、轴突分支或树突棘形成。PRGs 高度特异于脑,属于类脂磷酸磷酸酶(LPPs)超家族,通过生物活性脂质的去磷酸化来影响脂质代谢。然而,PRGs 本身没有酶活性,但以仍在研究中的方式修饰脂质代谢。
我们分析了小鼠大脑发育过程中、海马体、新皮层、嗅球和小脑所有 Prgs 的 mRNA 表达水平。我们发现每个 Prg 都有不同的时空表达模式,并在整个脑发育过程中发现了未被表征的 Prg4 的高表达。与它的近亲 PRG3 和 PRG5 不同,PRG4 不会诱导非神经元细胞系中的丝状伪足生长,也不会定位于丝状伪足的质膜。
我们表明 PRG4 在发育中和成年脑中高度表达,表明它对正常脑功能至关重要。尽管它与其他家族成员有相似之处,但它似乎不参与细胞形态的变化;相反,它更可能与细胞内信号转导有关。