关键词: CO2 HCO3-sensing astrocyte expression central nervous system gene variants mouse hippocampus neuronal expression receptor protein tyrosine phosphatase (RPTP) γ and ζ

来  源:   DOI:10.3389/fphys.2024.1406448   PDF(Pubmed)

Abstract:
Receptor protein tyrosine phosphatases γ and ζ (RPTPγ and RPTPζ) are transmembrane signaling proteins with extracellular carbonic anhydrase-like domains that play vital roles in the development and functioning of the central nervous system (CNS) and are implicated in tumor suppression, neurodegeneration, and sensing of extracellular [CO2] and [HCO3 -]. RPTPγ expresses throughout the body, whereas RPTPζ preferentially expresses in the CNS. Here, we investigate differential RPTPγ-RPTPζ expression in three sources derived from a wild-type laboratory strain of C57BL/6 mice: (a) mixed neuron-astrocyte hippocampal (HC) cultures 14 days post isolation from P0-P2 pups; (b) P0-P2 pup hippocampi; and (c) 9- to 12-week-old adult hippocampi. Regarding RPTPγ, we detect the Ptprg variant-1 (V1) transcript, representing canonical exons 1-30. Moreover, we newly validate the hypothetical assembly [XM_006517956] (propose name, Ptprg-V3), which lacks exon 14. Both transcripts are in all three HC sources. Regarding RPTPζ, we confirm the expression of Ptprz1-V1, detecting it in pups and adults but not in cultures, and Ptprz1-V3 through Ptprz1-V7 in all three preparations. We newly validate hypothetical assemblies Ptprz1-X1 (in cultures and pups), Ptprz1-X2 (in all three), and Ptprz1-X5 (in pups and adults) and propose to re-designate them as Ptprz1-V0, Ptprz1-V2, and Ptprz1-V8, respectively. The diversity of RPTPγ and RPTPζ splice variants likely corresponds to distinct signaling functions, in different cellular compartments, during development vs later life. In contrast to previous studies that report divergent RPTPγ and RPTPζ protein expressions in neurons and sometimes in the glia, we observe that RPTPγ and RPTPζ co-express in the somata and processes of almost all HC neurons but not in astrocytes, in all three HC preparations.
摘要:
受体蛋白酪氨酸磷酸酶γ和ζ(RPTPγ和RPTPζ)是具有细胞外碳酸酐酶样结构域的跨膜信号蛋白,在中枢神经系统(CNS)的发育和功能中起着至关重要的作用,并与肿瘤抑制有关。神经变性,和胞外[CO2]和[HCO3-]的传感。RPTPγ在全身表达,而RPTPζ优先在CNS中表达。这里,我们研究了来自C57BL/6小鼠野生型实验室品系的三种来源的RPTPγ-RPTPζ表达差异:(a)从P0-P2幼崽分离后14天的混合神经元-星形胶质细胞海马(HC)培养物;(b)P0-P2幼崽海马;(c)9至12周龄的成年海马。关于RPTPγ,我们检测到Ptprg变体1(V1)转录本,代表规范外显子1-30。此外,我们新验证了假设的程序集[XM_006517956](建议名称,Ptprg-V3),缺少第14外显子.两种转录物都在所有三个HC来源中。关于RPTPζ,我们证实了Ptprz1-V1的表达,在幼犬和成虫中检测到它,但在培养物中没有,和Ptprz1-V3至Ptprz1-V7在所有三种制剂中。我们新验证了假设的组件Ptprz1-X1(在文化和幼崽中),Ptprz1-X2(在所有三个中),和Ptprz1-X5(幼犬和成年),并建议将其分别重新指定为Ptprz1-V0,Ptprz1-V2和Ptprz1-V8。RPTPγ和RPTPζ剪接变体的多样性可能对应于不同的信号功能,在不同的细胞区室,在发展过程中与以后的生活。与以前的研究报告不同的RPTPγ和RPTPζ蛋白在神经元和有时在神经胶质中表达相反,我们观察到RPTPγ和RPTPζ在几乎所有HC神经元的躯体和过程中共表达,但在星形胶质细胞中不表达,在所有三种HC制剂中。
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