SLMAP3 is crucial for organogenesis through mechanisms involving primary cilia formation.

IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Open Biology Pub Date : 2024-10-01 Epub Date: 2024-10-17 DOI:10.1098/rsob.240206
Ana Paula Dias, Taha Rehmani, Billi Dawn Applin, Maysoon Salih, Balwant Tuana
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引用次数: 0

Abstract

SLMAP3 is a constituent of the centrosome and is known to assemble with the striatin-interacting phosphatase and kinase (STRIPAK) complex, where it has been reported to repress Hippo signalling. The global knockout of SLMAP3 in mice results in embryonic/perinatal lethality and stunted growth without changes in the phosphorylation status of YAP. Diverse phenotypes present in the SLMAP3-/- embryos include reduced body axis, small and abnormal organs resembling defects in planar cell polarity (PCP) signalling, while also displaying the notable polycystic kidneys, a known manifestation of ciliopathies. Analysis of cell polarity in primary mouse embryonic fibroblasts (MEFs) including cell migration, orientation and mitotic spindle angle did not reveal any changes due to SLMAP3 loss in these cells, although the expression of DVL3 was significantly reduced. Furthermore, MEFs lacking FGFR1OP2 or STRN3, two other STRIPAK members, did not reveal any significant changes in any of these parameters either. Significant changes in the number of ciliated cells and primary cilium length in SLMAP3 and FGFR1OP2 deficient MEFs were evident, while a reduced primary cilium length was notable in chondrocytes of SLMAP3 deficient embryos. Our findings suggest that SLMAP3 is essential for mouse embryogenesis through novel mechanisms involving the primary cilium/PCP and protein stability independent of Hippo signalling.

SLMAP3 通过涉及初级纤毛形成的机制对器官形成至关重要。
SLMAP3 是中心体的组成成分,已知可与纹蛋白相互作用磷酸酶和激酶(STRIPAK)复合物组装在一起,据报道可抑制 Hippo 信号。在小鼠中全面敲除 SLMAP3 会导致胚胎/围产期死亡和生长迟缓,但 YAP 的磷酸化状态不会发生变化。SLMAP3-/-胚胎的表型多种多样,包括体轴缩短、器官小且异常,类似于平面细胞极性(PCP)信号缺陷,同时还表现出显著的多囊肾,这是纤毛虫病的一种已知表现形式。对原代小鼠胚胎成纤维细胞(MEFs)的细胞极性(包括细胞迁移、定向和有丝分裂纺锤体角度)进行分析后发现,这些细胞并没有因为 SLMAP3 的缺失而发生任何变化,但 DVL3 的表达却显著减少。此外,缺乏另外两种 STRIPAK 成员 FGFR1OP2 或 STRN3 的 MEF 也没有发现这些参数有任何显著变化。在 SLMAP3 和 FGFR1OP2 缺乏的 MEF 中,纤毛细胞数量和初级纤毛长度发生了明显变化,而在 SLMAP3 缺乏的胚胎软骨细胞中,初级纤毛长度明显减少。我们的研究结果表明,SLMAP3 通过涉及初级纤毛/PCP 和蛋白稳定性的新机制对小鼠胚胎发育至关重要,而这些机制与 Hippo 信号无关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Open Biology
Open Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
10.00
自引率
1.70%
发文量
136
审稿时长
6-12 weeks
期刊介绍: Open Biology is an online journal that welcomes original, high impact research in cell and developmental biology, molecular and structural biology, biochemistry, neuroscience, immunology, microbiology and genetics.
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