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Sara 的磷酸化状态控制着有丝分裂过程中末期从中心纺锤体的输出。

Sara phosphorylation state controls the dispatch of endosomes from the central spindle during asymmetric division.

机构信息

Department of Biochemistry, University of Geneva, Geneva 1211, Switzerland.

出版信息

Nat Commun. 2017 Jun 6;8:15285. doi: 10.1038/ncomms15285.

DOI:10.1038/ncomms15285
PMID:28585564
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5467175/
Abstract

During asymmetric division, fate assignation in daughter cells is mediated by the partition of determinants from the mother. In the fly sensory organ precursor cell, Notch signalling partitions into the pIIa daughter. Notch and its ligand Delta are endocytosed into Sara endosomes in the mother cell and they are first targeted to the central spindle, where they get distributed asymmetrically to finally be dispatched to pIIa. While the processes of endosomal targeting and asymmetry are starting to be understood, the machineries implicated in the final dispatch to pIIa are unknown. We show that Sara binds the PP1c phosphatase and its regulator Sds22. Sara phosphorylation on three specific sites functions as a switch for the dispatch: if not phosphorylated, endosomes are targeted to the spindle and upon phosphorylation of Sara, endosomes detach from the spindle during pIIa targeting.

摘要

在不对称分裂过程中,母细胞中决定子细胞命运的物质通过母体决定子的分配来实现。在果蝇感觉器官前体细胞中,Notch 信号通过 Sara 内体被内吞进入母细胞,随后它们首先被靶向到中心纺锤体,在那里它们被不对称地分配,最终被分配到 pIIa 中。虽然内体靶向和不对称的过程开始被理解,但最终被分配到 pIIa 的机制尚不清楚。我们发现,Sara 结合了 PP1c 磷酸酶及其调节因子 Sds22。Sara 在三个特定位点的磷酸化作用是一个开关,用于进行分配:如果不磷酸化,内体就会被靶向到纺锤体上,而当 Sara 磷酸化时,内体在 pIIa 靶向过程中会从纺锤体上脱离。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffb/5467175/3b5e94b97788/ncomms15285-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffb/5467175/9e0f538e1f84/ncomms15285-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffb/5467175/82902100e991/ncomms15285-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffb/5467175/e1d6b7fcda27/ncomms15285-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffb/5467175/37bbb0729b25/ncomms15285-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffb/5467175/46ea3a4e676b/ncomms15285-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffb/5467175/3b5e94b97788/ncomms15285-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffb/5467175/9e0f538e1f84/ncomms15285-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffb/5467175/82902100e991/ncomms15285-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffb/5467175/e1d6b7fcda27/ncomms15285-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffb/5467175/37bbb0729b25/ncomms15285-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffb/5467175/46ea3a4e676b/ncomms15285-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cffb/5467175/3b5e94b97788/ncomms15285-f6.jpg

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Nature. 2015 Aug 27;524(7566):489-92. doi: 10.1038/nature14496. Epub 2015 Jul 13.
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Directional Notch trafficking in Sara endosomes during asymmetric cell division in the spinal cord.脊髓不对称细胞分裂过程中 Sara 内涵体中的定向 Notch 运输。
Commun Biol. 2024 Apr 10;7(1):439. doi: 10.1038/s42003-024-06018-7.
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Asymmetric Notch activity by differential inheritance of lysosomes in human neural stem cells.人神经干细胞中溶酶体差异遗传导致非对称 Notch 活性。
Sci Adv. 2022 Feb 11;8(6):eabl5792. doi: 10.1126/sciadv.abl5792.
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Fine-Tuning the TGFβ Signaling Pathway by SARA During Neuronal Development.在神经元发育过程中,SARA对转化生长因子β信号通路的精细调控。
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The exocyst complex and Rab5 are required for abscission by localizing ESCRT III subunits to the cytokinetic bridge.外核体复合物和 Rab5 需要将 ESCRT III 亚基定位到胞质分裂桥,才能完成胞质分裂。
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